Evaluation of The Prognostic Role of Sox2 as A Tumor Stem Cell Marker in Odontogenic Cysts and Tumors: Clinical, Radiographic and Immunohistochemical Correlation

Evaluation of The Prognostic Role of Sox2 as A Tumor Stem Cell Marker in Odontogenic Cysts and Tumors: Clinical, Radiographic and Immunohistochemical Correlation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluation of The Prognostic Role of Sox2 as A Tumor Stem Cell Marker in Odontogenic Cysts and Tumors: Clinical, Radiographic and Immunohistochemical Correlation Haneen Mahmoud, Mohamed Abdel-Monem Tawfik, Sherif Yousef Elnagdy, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6248573/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Nov, 2025 Read the published version in BMC Oral Health → Version 1 posted 10 You are reading this latest preprint version Abstract Background Odontogenic cysts and tumors are highly encountered jaw lesions with varying clinical characteristics and disease behavior. Its pathogenesis may involve the existence of tumor stem cells. SOX2 transcription factor is expressed in embryonic and adult stem cells and exerts a potent influence on maintaining pluripotency. SOX2 expressing cells would account for the aggressive nature and recurrence of some odontogenic pathologies. To evaluate the prognostic role of SOX2 stem cell marker in odontogenic cysts and tumors and determine whether its expression is associated with the clinico-biological behavior of these lesions, this study aimed to assess the immunoexpression of the stem cell marker SOX2 in ameloblastoma, odontogenic keratocyst and dentigerous cyst and correlate SOX2 immunohistochemical staining scores to clinical and radiographic findings and recurrence of these lesions. Methods Forty-Five s urgical specimens were included in this study, 15 ameloblastomas (Ab), 15 odontogenic keratocysts (OKC) and 15 dentigerous cysts (DC). An immunohistochemical (IHC) study using the SOX2 Rabbit Polyclonal Antibody was done to evaluate SOX2 expression. A semi-quantitative method for subjectively scoring percentage and intensity of SOX2 staining was carried out. Statistical correlation to clinical data, radiological findings and recurrence were analyzed. Results Nuclear SOX2 expression was strong positive within OKC specimens in both basal and sub-basal layers, followed by Ameloblastoma which showed nuclear and cytoplasmic reaction, while most cases of DC recorded low positive scores. Significant difference in SOX2 (IHC) staining scores was found between (OKC) and (DC) (P = < 0.001*), as well as between (Ab) and (DC) (P = 0.012*), (OKC) showed a significant higher SOX2 expression than ameloblastoma (P = 0.048*). A significant positive correlation was found between SOX2 expression and both cortical bone perforation and recurrence (P = 0.040*, 0.001*), while no significant correlation to age, gender, root resorption or radiographic loculation (P = 0.874, 0.162, 0.062, 0.137). Conclusion SOX2 is a reliable marker for tumor stem cells (TSCs) within benign odontogenic lesions. Positive correlation of SOX2 expression to cortical bone perforation and recurrence of these lesions point to the aggressive biological behavior, clinical outcome and poor prognosis. The prognostic role of SOX2 is of great value to improve treatment of odontogenic lesions. Trial registration This study was registered in ClinicalTrials.gov PRS (https//register.clinicaltrials.gov) under identification number NCT06833840 on 01/21/2025. SOX2 Odontogenic keratocyst Ameloblastoma Dentigerous cyst Immunohistochemistry Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Odontogenic cysts and tumors are among the most often observed pathological lesions in the head and neck region, which can be defined as clinico-pathological entities with inherent degrees of biological aggressiveness and wide range of disease behavior. ( 1 ) Considerable variation in the clinicopathologic features can sometimes be challenging and increase the chance of misdiagnosis. The prognosis of these lesions varies depending on their biological behavior, recurrence potential and treatment approach; Some lesions have excellent outcomes when diagnosed early, while others are aggressive and require long term follow up. ( 2 ) Ameloblastoma (Ab) is the most common odontogenic epithelial tumor, accounting for 9–11% of odontogenic tumors. ( 3 ) It is represented by slow growth, asymptomatic swelling and/or perforation of the cortical bone and might grow into massive proportions causing facial deformity. ( 4 ) Although Ab is a benign odontogenic tumor of jawbones, it is characterized by its aggressive local invasion and high recurrence incidence up to 55%-90%, which necessitate precise histological diagnosis and radical surgical treatment. Additionally, few reports of distant metastatic ameloblastomas were documented. ( 5 , 6 ) The high level of tumor stem cells in Ab may represent a cause for tumor recurrence. ( 7 ) Odontogenic Keratocyst (OKC) is a distinctive type of odontogenic cysts with an aggressive clinical potential and high recurrence rate (25–60%). (8) It differs from typical cysts in growth pattern and biological behavior, its growth is triggered by the active proliferation of the epithelial lining rather than the osmotic pressure of the cystic fluid. As OKC grows through extension rather than expansion, it develops antero-posteriorly with limited initial indication of cortical expansion. The destructive nature of OKC and recurrence potential has many theories for the cyst to be consider a tumor. ( 9 ) Another common cyst of non-inflammatory odontogenic origin, is the Dentigerous cyst that arises from the pericoronal tissue of an impacted tooth. ( 10 ) Clinically, DCs are often asymptomatic and could be diagnosed incidentally during an oral check-up, but may occasionally cause enormous swelling and dental displacement. Radiographically, they may resemble an OKC or an Ab. DC has good prognosis and rarely recurs, however radiolucencies greater than 4 mm are thought to indicate more aggressive behavior, which can result in tooth displacement. ( 11 ) A set of genetic and molecular alterations are involved in the pathogenesis, progression and clinical behavior of odontogenic lesions. The exact mechanism remains unclear, recent studies suggest that it may be evolved by a stem cell population called the tumor stem cells (TSCs) or cancer stem cells (CSCs). ( 12 ) SOX2 is a characteristic member of the SOX family of transcription factors, which is considered a subpopulation of stemness-related genes. It is essential for early development, maintenance and self-renewal of undifferentiated stem cells. It is evident in embryonic and adult stem cells, and play an essential role in maintaining pluripotency. ( 13 ) It has been found to be related to oncogenic signaling pathways, controlling tumor cells by affecting their fate, proliferation and apoptosis. ( 14 ) SOX2 is a principle marker for dental epithelial and mesenchymal stem cells associated with tooth renewal and replacement. ( 15 ) Recent studies indicate that sox2 can be a potential novel biomarker to distinguish between malignant, and benign lesions as it is a specific and sensitive marker for high-grade lesions. Furthermore, it has been linked to the process of tumor initiation, destructive clinical course and poor prognosis. ( 16 ) Variable SOX2 expression was noted in different types of benign and malignant neoplasms. ( 15 , 17 , 18 ) This has been linked to the stem-like characteristics of tumor cells. Poor patient prognosis was associated with elevated SOX2 expression in cancers of the oral cavity, esophagus, breast, liver, rectal and prostate. ( 19 ) Available data in literature suggest that SOX2 is expressed differently in odontogenic cysts and tumors which may reflect their different histogenesis, however, few research correlate SOX2 expression to clinical and radiological findings in benign odontogenic cysts and tumors. Predicting biological behavior and prognosis of these common lesions will greatly aid in patient management and improve treatment outcomes. In order to evaluate the prognostic role of the stem cell marker SOX2, and determine whether its expression in Ab, OKC, and DC is associated with the clinico-biological behavior of these lesions, this study aimed to assess the immunoexpression of SOX2 in these tissues and correlate SOX2 immunohistochemical staining score to clinical data, radiographic findings and recurrence ratio. Methods Patient selection Forty-Five patients diagnosed with benign odontogenic cysts or tumors (Ab, OKC and DC) either in maxilla or mandible and needed surgical treatment were selected from the Out-Patient Clinic of Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Mansoura University. No age or gender preference was specified in this study. Histopathological examination and immunohistochemistry (IHC) staining of tissue samples were done at Oral Pathology Department Faculty of Dentistry, Mansoura University. Ethics and Consent All patients were informed about the aim of the designed study, complete treatment plan and a written consent was obtained. The institutional Review Board (IRB) of the Faculty of Dentistry, Mansoura University, Mansoura, Egypt, approved the current study in compliance with the seventh revision of the Helsinki Declaration in 2013 under protocol number (No. A06010222). It is registered in Clinical-Trials.gov PRS ( https://register.clinicaltrials.gov ) under identification number NCT06833840 on 01/21/2025. Sample Size Calculation Sample size calculation was based on mean of SOX2 percentage area among ameloblastoma and odontogenic keratocyst obtained from previous research. ( 20 ) Using G*power version 3.1.9.4 ( 21 ) to calculate sample size based on effect size of 1.9333975, 2-tailed test, α error = 0.05 and power = 95.0% then a sample of 15 cases per group would be required. Study Design This is a prospective immunohistochemical study through which fifty-five patients with suspected odontogenic cysts or tumors underwent further clinical and radiographic assessment. Incisional or excisional biopsy was carried out according to the lesion size and site, histopathological diagnosis of all tissue specimens to confirm lesion type was done based on 2022 WHO Classification of Head and Neck cysts and tumors. ( 22 ) After exclusion of non-eligible lesions, forty-five specimens were included in this study and were divided into 3 groups: Group A: including 15 cases of Ameloblastoma (Ab). Group B: including 15 cases of Odontogenic Keratocyst (OKC). Group C: including 15 cases of Dentigerous Cyst (DC). Surgical Procedures After detailed data collection, a complete clinical and radiographic examination (Panoramic x-ray and Cone Beam Computed Tomography) was done for each patient. Lesion site, size, pattern of radiolucency, relation to anatomical landmarks and buccal or lingual cortical bone perforation were assessed. An incisional or excisional biopsy was obtained according to the lesion size, the tissue specimens were fixed in 10% neutral formalin and were sent to the Oral Pathology Department, Faculty of Dentistry, Mansoura University where it was preserved into paraffin blocks and histopathologically diagnosed using hematoxylin and eosin staining. According to the diagnosis of each lesion, suitable surgical intervention including marsupialization followed by enucleation, enucleation and curettage, marginal or segmental resection were utilized in the management of different cases in this study. Immunohistochemical marker Rabbit Polyclonal Antibody for Sex-determining region Y (SRY)-box 2(SOX2), BIOCYC Gesellschaft für Biotechnologie, Germany (Catalog No. 2-SO108-13, 7 ml Ready-to-use). Immunohistochemical staining ( 23 ) Sections of 4 µ thickness were cut from paraffin blocks, mounted on negatively charged Opti plus slides for assessment of SOX2 using a universal kit (1.0 Poly HRP DAB Kit). After being deparaffinized in xylene, the sections were rehydrated in alcohol at decreasing concentrations. Antigen Retrieval was performed. After 10 minutes of immersion in citrate buffer PH6, the slides were heated, blocked for 30 minutes using 1.5% horse serum from "Santa Cruz Biotechnology," and then diluted in phosphate buffered solution (PBS). Incubation of primary antibodies of Rabbit Polyclonal Anti-SOX2 at room temperature (45min). Slides were washed with PBS (3 minutes). The slides were then incubated with the secondary antibody for 25 minutes at room temperature then were washed in PBS for 3 minutes. Slides were treated with streptavidin–biotin enzyme reagent “DAKO, Denmark” (10 minutes) and rewashed in PBS (3 minutes). To create color, drops of "3.3 Diaminobenzidine tetrahydrochloride" (DAB) were used as a chromogen. Mayers hematoxylin was used as a counterstain, and sections were fixed for three minutes using a mounting media based on xylene. Positive immune deposits were detected as brown spots. As positive control, Squamous Cell Carcinoma (SCC) was used for confirmation of the marker expression. Negative controls were prepared using non-immune serum. Evaluation of immunohistochemical staining Semi-quantitative method for subjectively scoring the immunohistochemical staining : Immunohistochemically stained sections were interpreted independently by two pathologists. The immune reactivity for SOX2 was assessed by a scoring system based on the both percentage and intensity of staining. ( 24 ) Specimens were considered to be positive for staining when the cells had a brown nucleus. Immune reactivity was evaluated by scanning the slides under a light microscope at 200x magnification. Five fields were selected that were rich in lesional cells. The percentage of staining was graded from (0:4), 0 = negative, 1 = 1:25%, 2 = 26:50%, 3 = 51:75, and 4 = 76:100%. The intensity was interpreted from (0:3) as 0 = negative, 1 = weak, 2 = moderate and 3 = strong. The percentage and intensity scores were then added to obtain a total score , which ranged from 0 to 7. The cases were categorized into one of the following categories according to their overall scores: Negative expression = 0 points, Low expression = 1:3 points and High expression = 4:7 points. Clinical and Radiological correlation Statistical correlations of SOX2 immunohistochemical total staining scores to clinical data including patient age, sex and recurrence, and to radiological findings including lesion site, radiographic loculation pattern, root resorption and buccal or lingual cortical bone perforation were analyzed. Statistical Analysis Data was fed to the computer and analyzed using GraphPad Prism 8 (GraphPad Software). Normally distributed data were presented as mean, and standard deviation (SD) values, the One-way ANOVA followed by post hoc Tukey’s multiple comparison test were used to compare between them. While non-normally distributed data were presented as median, and range values, the Kruskal-Wallis test followed by post hoc Dunn's multiple comparisons test were used to compare between these groups. Chi-square tests of goodness of fit and independence were used to compare the categorical data groups. Spearman's rank correlation coefficient was used where the value r = − 1 means a perfect negative correlation and the value r = 1 means a perfect positive one. The significance of the results obtained was judged at the (0.05) level. Results I. Clinical Results: As shown in (Table 1 ); The mean patients age of Ab, OKC and DC groups were 33.80 ± 14.65, 32.67 ± 15.01, and 28.07 ± 10.87 years respectively with no statistical significant difference (P = 0.48). Twenty-seven patients (60%) were males while eighteen patients (40%) were females. The number of males and females in each group was provided in Table 1 , along with the corresponding percentages. Thirty-eight lesions were found in mandible with posterior mandible predominance (6 in anterior mandible and 32 in posterior mandible) while seven lesions were found in maxilla (2 in anterior maxilla and 5 in posterior maxilla). The distribution of number and percentage of lesions sites between groups were shown in (Table 1 ). The results showed no statistically significant difference in the maxillary and mandibular distributions among studied groups (p = 0.31). Five patients included in this study were received as recurrent cases, distributed as 3 (20%), 2 (13.3%), 0 (0%) among Ab, OKC and DC groups respectively. The histopathological assessment of recurrent cases of Ab revealed that 2 cases were conventional Ab of follicular histopathological variants, and the third case was unicystic Ab with mural histopathological variant. Table 1 Clinical data (patients age, sex, lesion site, patients received as recurrent) Sex Age Site Patients Received as recurrent Male n (%) Female n (%) Mean ± SD Maxilla Mandible Ant post n (%) n (%) Ant Post n (%) n (%) Ab 10 5 (66.7%) (33.3%) 33.80 ± 14.65 1 0 (6.6%) 4 10 (26.7%) (66.7%) 3 (20%) OKC 9 6 (60%) (40%) 32.67 ± 15.01 1 2 (6.6%) (13.3%) 0 12 (80%) 2 (13.3%) DC 8 7 (53.3) (46.7) 28.07 ± 10.87 0 3 (20%) 2 10 (13.3%) (66.7%) 0 Test P value X 2 = 0.556 P = 0.46 F = 0.743 P = 0.48 X 2 = 7.113 P = 0.31 X 2 = 3.15 P = 0.07 Ab: Ameloblastoma, OKC: Odontogenic keratocyst, DC: Dentigerous cyst, SD: standared deviation, Ant: Anterior, Post: Posterior, n = number of patients, X 2 : chi-square test, F: One way ANOVA, P: not significant (at level p < .05) II. Radiographic Results: 1- Radiographic locular pattern: Ab group had a higher percentage of multilocular radiolucencies (66.7%) compared to the OKC (26.7%) and DC (13.3%) groups. OKC and DS groups had higher percentages of unilocular radiolucencies (73.3% and 86.7%) compared to the Ab (33.3%) group. The results showed a statistically significant difference in locular pattern between the groups (p = 0.002*) (Table 2 , Fig. 1 ). Table 2 Radiographic features Loculation Bone Perforation N (%) Root resorption N (%) Unilocular N (%) Multilocular N (%) Ab 5 (33.3%) 10 (66.7%) 9 (60%) 8 (53.3%) OKC 11 (73.3%) 4 (26.7%) 2 (13.3%) 1 (6.7%) DC 13 (86.7%) 2 (13.3%) 0 (0%) 3 (20%) Test P value X 2 X 2 = 10.08 P = 0.002* X X 2 = 16.12 P = 0.0001* X 2 = 8.86 P = 0.003* Ab: Ameloblastoma, OKC: Odontogenic keratocyst, DC: Dentigerous cyst X 2 : Chi square test, *Statistically significant ( P ≤ 0.05) 2- Association of bone perforation: The Ab group had a higher percentage of cases associated with bone perforation (60%) compared to the OKC (13.3%) and DC groups (0%). The results revealed a significant difference in the association of bone perforation between the groups (p = 0.0001*) (Table 2 , Fig. 1 ). 3- Root resorption: Eight cases of Ab, one keratocyst and 3 dentigerous cysts were associated with root resorption in one or more of included teeth. The results revealed a significant difference in the association of root resorption between the groups (p = 0.003*) (Table 2 ). III. Histopathological results The histopathological assessment of Ab revealed 10 cases of conventional Ameloblastoma, which were subdivided into 5 follicular, 3 plexiform, 1 acanthomatous and 1 desmoplastic variants. In addition to 5 cases of unicystic ameloblastoma subdivided into 3 mural, 1 luminal and 1 intraluminal subtypes. (Fig. 2 : a-f). Histopathological features by H&E stain for keratocyst and dentigerous cyst were shown in (Fig. 4 a) and (Fig. 5 a). IV. Immunohistochemical results SOX2 staining score: Ameloblastoma Only one case showed negative immunoreaction. SOX2 gene expression was observed in fourteen cases of Ab with moderate to strong intensity. By calculating total score, 66.6% (10 cases) recorded high positive scores, 26.7% (4 cases) recorded low positive expression. (median of total score = 4) (Table 3 ). Table 3 SOX2 scores of staining percentage and intensity SOX2 staining percentage SOX2 intensity Total score score 0 score1 score2 score3 score4 score 1 score2 score 3 Negative Low High Ab 1 4 6 4 0 3 7 4 1(6.7%) 4 (26.7%) 10 (66.6%) OKC 0 2 8 5 0 1 3 11 0 1 (6.7%) 14 (93.3%) DC 0 10 5 0 0 10 5 0 0 13(86.7%) 2 (13.3%) P value 0.007* > 0.001* > 0.001* P value between groups P1 = 0.264 P2 = 0.044* P3 = 0.002* P1 = 0.022* P2 = 0.040* P3 = < 0.001* P1 = 0.048* P2 = 0.012* P3 = < 0.001* Ab: Ameloblastoma, OKC: Odontogenic keratocyst, DC: Dentigerous cyst Used test: Kruskal-Wallis test followed by post hoc Dunn's multiple comparisons test. *Statistically significant ( P ≤ 0.05) P1: significance between AB and OKC groups, P2: significance between AB and DC groups, and P3: significance between OKC and DC The expression was mainly nuclear in ameloblast like cells at the periphery of ameloblastic units, also large number of cases showed cytoplasmic expression which indicate more tumor aggressiveness. (Fig. 3 a-f). OKC : The SOX2 expression was detected in basal and suprabasal layers of all cases with high positive expression in 14 cases (93.3%) and only one case showed low positive expression (6.7%), (median of total score = 5) (Fig. 4 : b-d) DC Weak to moderate intensity of SOX2 expression was observed in the cytoplasm of basal and supra-basal layers (Fig. 5 b-c). By calculating total score, SOX2 expression was low positive in 13 cases (86.7%) and 2 cases recorded high positive expression (13.3%), (median of total score = 3) (Table 4 ) Table 4 Correlation of SOX2 IHC staining scores to clinical & radiographic findings Correlation with SOX2 IHC staining score Spearman's rank correlation coefficient (r) P-value Age 0.0242 0.874 Gender -0.2417 0.162 Recurrence 0.467 0.001* Root resorption 0.2807 0.062 Radiographic loculation 0.225 0.137 Bone perforation 0.307 0.040* *Statistically significant ( P ≤ 0.05) Statistical analysis showed significant difference in SOX2 expression between Ab and DC (P = 0.012) and between OKC and DC (P = < 0.001). Additionally, OKC recorded a significantly higher SOX2 expression than Ab (P = 0.048) V. Correlation results Correlation of SOX2 IHC staining scores to clinical & radiographic findings revealed a non-statistically significant correlation to age and gender, non-significant positive correlation to root resorption and multilocular radiolucency pattern. While it revealed significant medium positive correlation to bone perforation (P = 0.04) and a significant high positive correlation to recurrence (P = 0.001). (Table 4 ). Discussion Recent studies suggest that tumor Stem cells play a crucial role in the initiation, progression, aggressiveness and recurrent nature of odontogenic cysts and tumors. ( 2 , 19 , 20 ) This study aimed to assess the prognostic role of SOX2 as a tumor stem cell marker in odontogenic cysts and tumors; it is one of the primary studies which correlate SOX2 immunohistochemical staining scores to different clinical and radiological findings in these common pathologies. The lesions investigated in this study were ameloblastoma and odontogenic keratocyst, as they possess great clinical interest due to their aggressive biological behavior and tendency to recurrence, and the dentigerous cyst (DC) as it is the most common developmental odontogenic cyst. The expression of stem cell marker was documented via immunohistochemistry as it is considered the gold-standard for the detection of the tissue-specific expression of proteins and their precise subcellular localization. ( 25 ) In this study, 15 cases of both conventional and unicystic Ab were assessed, follicular form was the most recorded pathological variant followed by Plexiform. SOX2 gene expression was observed in all studied Ab cases except one case of unicystic type. These findings are in accordance with Pagella et al.,2020 ( 26 ) who reported the widespread expression of the dental epithelial stem cell marker SOX2 within Ameloblastomas, suggested that a major proportion of the cells composing these tumors present Cancer stem cells-like properties and would explain its aggressive behavior. Most of the included Ab specimens showed moderate to high SOX2 intensity. As regards SOX2 IHC total scores; 10 cases showed high positive scores and 4 cases recorded low positive scores. The expression was mainly nuclear in ameloblast like cells at the periphery of ameloblastic units, but also large number of cases showed nuclear and cytoplasmic expression. According to van Schaijik et al.,2018 ( 27 ) this cytoplasmic expression of SOX2 could be an indicator of more tumor aggressiveness. Results of this study are in accordance with Jurri et al , ( 28 ) who reported that SOX2 was expressed in the epithelial cells of follicular and plexiform ameloblastoma diffusely, suggesting that SOX2 functions in maintaining the progenitor state of epithelium in ameloblastoma. A statistically significant higher SOX2 expression in Ab than dentigerous cyst was recorded in this study (P = 0.012). This result resembles the findings by Balbinot et al., 2023 , ( 29 ) as they reported a greater expression of SOX-2 in Ab in relation to the DC lining epithelium and dental follicle (DF) epithelial nests. On the other hand, de Freitas Silva et al 2020 ( 30 ) and Bandyopadhyay et al., 2017 ( 31 ) investigations revealed that SOX2 was not expressed in Ab specimens. Phattarataratip et al., 2021 ( 17 ) recorded mild to moderate SOX2 expression, limited to the ameloblast like cells in ameloblastoma. The conflicting results in literature regarding SOX2 expression pattern in ameloblastomas are most likely due to using different antibodies. This variable SOX2 expression pattern in ameloblastomas may suggest that additional molecular mechanism could be responsible for the neoplastic characteristics of this specific odontogenic tumor. As regards OKC cases in this study, the SOX2 expression was detected in basal and suprabasal layers of all cases with high positive expression in 14 cases and only one case showed low positive expression. This result is in accordance with Bandyopadhyay et al., 2017 ( 31 ) , de Freitas Silva et al., 2020 ( 30 ) and Pereira et al., 2023 ( 32 ) in which all cases showed patent SOX2 expression in all layers of OKC. Throughout the current analysis, the entire thickness of the OKC epithelial lining had SOX2 staining, which may suggest that all cell layers of OKC specimens retain the progenitor characteristics of odontogenic epithelium, displaying a stem cell-like phenotype and ongoing proliferation. According to de Freitas Silva et al ( 30 ) this could suggest that OKC displays keratinocyte differentiation, and validate the epithelium's basal and suprabasal layers' OKC cells' capacity for dedifferentiation. High SOX2 expression in OKC as found in our study may explain the high mitotic activity and aggressive nature of the lesion and point to the imbalance between cell growth and cell death in OKC, which could be a sign of neoplastic attitude and the unusually higher recurrence rate of OKCs than other jaw cysts. These findings provide a rationale for the reclassification of this entity as a tumor. A statistically significant difference in SOX2 expression was found between OKC and Ab (P = 0.048), as well as DC (P = < 0.001). This was similar to de Freitas Silva et al., 2020 ( 30 ) and Pereira et al., 2023 ( 32 ) as they recorded that SOX2 immunoreactivity was statically significant in OKC cases compared to Ab cases. Phattarataratip et al., 2021 ( 17 ) showed that most OKC (86.7%) expressed high SOX2 expression in more than 50% of epithelial cells, significantly higher than ameloblastoma. This difference may be related to their diverse cells of origin or stage of histogenesis. In the current study, DC showed low to moderate SOX2 intensity. IHC scores were low in 13 cases of DC, while only two cases were highly positive. This result is similar to Balbinot et al., 2023 ( 29 ) where all 10 cases of DC showed low positive expression. Furthermore, Phattarataratip et al., 2021 ( 17 ) recorded minimal to no SOX2 expression in DC cases . This proves the fact that DC is not aggressive in its biological behavior, as it is generally accepted that DC is developed from the accumulation of fluid between the reduced enamel epithelium and the crown of an unerupted tooth, while OKC is believed to be derived from the remnants of dental lamina. Regarding clinical correlations, the mean age of included patients in Ab, OKC & DC groups was 33.80 ± 14.65, 32.67 ± 15.01, and 28.07 ± 10.87 respectively. This was in accordance with the globally reported peak of incidence as reported in many studies. ( 33 – 36 ) Statistically, there was non-significant correlation between IHC scores and patient age (P = 0.874). Concerning gender domination, the results of this study displayed that males are more affected than females in all studied groups; Ab, OKC and DC as the percentage of male patients was 66.7%, 60% and 53.3% respectively. This result seems in line with other studies, ( 37 – 40 ) but in contrast with some results in literature ( 41 ) which showed no sex predilection in Ab, OKC and DC. Correlation was not statistically significant between IHC scores and patient gender (P = 0.162) In the current work, the most affected site in Ab, OKC and DC was posterior mandibular area with percentage 66.7%, 80% and 66.7% respectively. This result is compatible with most of the reported results in the literature. ( 42 – 44 ) This predominance of posterior mandible may be due to its abundant blood supply, which provides tumors with the oxygen and nutrients they need for survival. ( 45 ) Five cases were received as recurrent in our study; 3 recurrent cases were Ab, representing 20% of the group. This result is in line with Lei et al., 2024 ( 18 ) and Bwambale et al., 2021 ( 33 ) studies, in which the recurrence rate was 17.2% and 23.2% respectively. However, Yang et al., 2017 ( 46 ) reported a recurrence rates of 9.8%. In association with histopathological patterns, the recurrent cases in this study were more in follicular variant which agrees with Goh et al., 2021 ( 38 ) and Hresko et al., 2022 . ( 47 ) In contrast, Bwambale et al., 2021 ( 33 ) reported that plexiform pattern had a higher recurrence rate. According to Au et al., 2019 ( 48 ) , there is no correlation between histological patterns and ameloblastoma recurrence. Among OKC group, 2 cases were received as recurrent with percentage 13.3%. This percentage is similar to Rahman et al., 2019 . ( 49 ) High recurrence rate may be due to the presence of satellite cysts and the thin cystic epithelium ,which has a lower tensile strength than other maxillofacial tumors, making it challenging to remove the tumor entirely in toto. ( 50 , 51 ) Additionally, dedifferentiation of the basal and suprabasal cells in OKC may be the cause of satellite cyst-induced recurrence. ( 31 , 32 ) A significant positive correlation was found between IHC scores and recurrence (P = 0.001) as the specimens of recurrent cases showed strong SOX2 overexpression. Similarly, Tseng et al., 2022 , ( 52 ) found that recurrent cases of Ab showed much higher labeling indices of SOX2 than paired primary lesions, and proposed that recurrence of Ab is associated with the presence of SOX2-expressing stem cells, as some tumor nests might be remained when the tumor was not adequately removed, SOX2 expressing cells remaining in these nests might give rise to the recurrent disease. Vanner et al. ( 53 ) showed that the SOX2 cells were quiescent in comparison to other tumor cells that cycled quickly, and that these SOX2 cells cause tumor regrowth following therapy. Regarding radiographic results, 66.67% of the Ab showed multilocular radiolucency, these results were comparable to the radiographic image reported in Smit et al., 2024 ( 34 ) and Malik et al., 2018. ( 54 ) Boffano et al., 2021 ( 55 ) mentioned that multilocular radiographic appearance of Ab was associated with high risk of recurrence. In this study, 73.3% of OKC patients and 86.7% of DC cases had clearly defined unilocular radiolucency, which is consistent with findings of Rahman et al 2019 , ( 49 ) and Terauchi et al., 2019. ( 56 ) However some big cysts exhibit a multilocular picture on panoramic radiographs, which is believed to be caused by the persistence of bone trabeculae within the radiolucency. ( 57 ) No significant correlation was found between SOX2 expression and the radiographic locular pattern of lesions in this study (P = 0.137), as well as root resorption of included teeth (P = 0.062). Current study showed cortical bone perforation in 60% of Ab cases in computed tomography x-ray (CBCT) which agrees with Smit et al., 2024 ( 34 ) who recorded cortical perforation in 77% of cases, this high percent points to the aggressiveness of this lesion. Two cases showed bone perforation in OKC, which demarcated the growth behavior of these lesions as the OKCs develop anteroposteriorly with little initial sign of cortical expansion. ( 58 ) However, other studies reported higher incidence of bone perforation associated with keratocyst (71.4%). ( 59 ) A significant correlation was found between SOX2 and cortical bone perforation (P = 0.04). This result is in accordance with Carneiro et al ( 59 ) , who correlated the imaging aspects of odontogenic cysts and tumors in CBCT to the lesion behavior, and reported that cortical perforation is the most indicative factor of an aggressive behavior. His results similarly to ours showed that aggressive lesions including ameloblastoma and keratocyst were highly associated with cortical bone perforation while among the non-aggressive lesions, the dentigerous cyst was not associated with cortical perforation. Fidele et al ( 60 ) reported that Enucleation of keratocysts combined with cortical perforation was statistically associated with high recurrence rate. All these findings which observed a strong positive expression of SOX2 transcription factor in OKC and Ab suggest that these lesions have cells with characteristics of cancer stem cells (CSs) that could be related to the progression and recurrence of these aggressive odontogenic pathologies. To sum up, this study showed that SOX2 expression is a valid indicator of the stem cell populations in odontogenic cysts and tumors. These cells have the capacity for self-renewal and pluripotency, which would account for the aggressive nature and recurrence of Abs and OKCs. Additionally, this study recorded correlation of SOX2 expression to cortical bone perforation and recurrence of these lesions which point to the biological behavior of these lesions, clinical outcome and poor prognosis. Predicting the prognosis of such aggressive lesions provides great value in patient management, avoiding recurrence, lowering patient morbidity and improving the treatment outcome. Conclusion This study clarified the diagnostic and prognostic relevance of SOX2 tumor stem cell marker in odontogenic cysts and tumors. A strong positive expression of SOX2 transcription factor was observed in OKC and Ab, suggesting that these lesions have cells with characteristics of cancer stem cells (CSs) that could be related to the progression and recurrence of these aggressive odontogenic pathologies. Positive correlation of SOX2 expression to cortical bone perforation and recurrence of these lesions points to the aggressive biological behavior, clinical outcome and poor prognosis. Recognizing such factors is of great value to improve treatment outcome of odontogenic lesions. Further studies with a larger study population and more than one marker are recommended. Abbreviations TSCs Tumor stem cells SOX-2 sex-determining region Y (SRY)-box 2 Ab Ameloblastomas OKC Odontogenic Keratocyst DC Dentigerous cyst IHC Immunohistochemical OTs Odontogenic tumors OPG panoramic X-ray CSCs Cancer stem cells IRB The Institutional Review Board PBS phosphate buffered solution DAB Diaminobenzidine tetrahydrochloride SCC Squamos cell carcinoma DF dental follicle Declarations Authors’ contributions Haneen Mahmoud Zeen El-Abdeen : Performing the Surgical Procedures, Formal Analysis, Data Curation. Mohamed Abdel-Monem Tawfik : Conceptualization, Supervision, Project Administration, Approving Final Manuscript. Sherif Yousef Elnagdy : Histopathological examination and immunohistochemistry of tissue samples,Reviewing and Editing the Final Manuscript. Noha Ahmed Mansour: Conceptualization, Interpretation of Data, Writing the Original Draft, Approving Final Manuscript. Availability of data and materials: The corresponding author can provide the data sets utilized and/or analyzed for this study upon reasonable request . Ethics approval: The institutional Review Board (IRB) of the Faculty of Dentistry, Mansoura University, Mansoura, Egypt, approved the current study in compliance with the seventh revision of the Helsinki Declaration in 2013 under protocol number (No. A06010222). Informed consent: According to the guidelines of Mansoura University institution’s ethics committee, each participant signed a written informed consent form for participation in this study. Consent for publication : Not applicable. Conflict of interests: The authors declare no conflict of interests Funding: The authors received no funding for this research. References Banerjee A, Kamath VV, Sundaram L, Krishnamurthy SSJJOS. OCT4 and SOX2 are reliable markers in detecting stem cells in odontogenic lesions. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6248573","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442147085,"identity":"593c8c59-ea0d-4724-ad0d-fddc2a9eef9a","order_by":0,"name":"Haneen Mahmoud","email":"data:image/png;base64,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","orcid":"","institution":"Mansoura University","correspondingAuthor":true,"prefix":"","firstName":"Haneen","middleName":"","lastName":"Mahmoud","suffix":""},{"id":442147086,"identity":"ebc31500-e818-4c2d-b9b2-0a12d727ec39","order_by":1,"name":"Mohamed Abdel-Monem Tawfik","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"Abdel-Monem","lastName":"Tawfik","suffix":""},{"id":442147087,"identity":"bbdcc3f3-4bf1-4b20-9c2c-2a99607f638e","order_by":2,"name":"Sherif Yousef Elnagdy","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Sherif","middleName":"Yousef","lastName":"Elnagdy","suffix":""},{"id":442147088,"identity":"51dbcc00-5a48-45cb-9c72-bd4f341b2ecf","order_by":3,"name":"Noha Ahmed Mansour","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Noha","middleName":"Ahmed","lastName":"Mansour","suffix":""}],"badges":[],"createdAt":"2025-03-18 02:23:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6248573/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6248573/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12903-025-07065-0","type":"published","date":"2025-11-01T15:58:15+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81941350,"identity":"9bc0e27a-caf6-4298-832f-f02db00f1b36","added_by":"auto","created_at":"2025-05-05 07:08:08","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":753893,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Panoramic x-ray of ameloblastoma shows multilocular radiolucency. (b) Panoramic x-ray of odontogenic keratocyst shows the unilocular radiolucency. (c) Panoramic x-ray of dentigerous cyst shows the unilocular radiolucency. (d) Axial view of CBCT shows lingual bone perforation in ameloblastoma. (e) Axial view of CBCT shows intact buccal and lingual cortex in Odontogenic keratocyst. (f) Axial view of CBCT shows intact bone cortex in Dentigerous cyst.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6248573/v1/941d05dffc15bb089e84d748.jpeg"},{"id":81940983,"identity":"1796dd60-c22e-4d84-9464-d8f3fddf63dd","added_by":"auto","created_at":"2025-05-05 07:00:08","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1105058,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhotomicrographs of histological subtypes of conventional and unicystic ameloblastoma. (H\u0026amp;E ×200)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a) Follicular ameloblastoma with odontogenic epithelial islands formed of peripheral columnal ameloblast like cells and central stellate reticulum like cells. (b) Plexiform ameloblastoma with anastomosing strands of odontogenic epithelium with scanty stroma. (c) Acanthomatous pattern of conventional ameloblastoma revealed squamous metaplasia of stellate reticulum-like cells. (d) Unicystic ameloblastoma luminal type revealing ameloblastomatous proliferation at the level of cystic epithelial lining. (e) Unicystic ameloblastoma intraluminal type with nodule of ameloblastomatous epithelium projecting inside the cystic cavity. (f) Mural subtype showing follicles of odontogenic epithelium presented in the cyst wall of odontogenic cyst.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6248573/v1/c8be3f9d2b7ce0723341bac7.jpeg"},{"id":81941349,"identity":"8a03612a-7b27-4f53-9aa2-1d08782a14ad","added_by":"auto","created_at":"2025-05-05 07:08:08","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1238187,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhotomicrographs of SOX2 expression in conventional and unicystic ameloblastoma. (ABC-DAB ×200)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a)Cytoblasmic expression of SOX2 in odontogenic epithelial follicles of follicular ameloblastoma. (b) Follicular ameloblastoma with microcystic formation with nuclear immunoreactivity for SOX2 mostly in the peripheral ameloblast like cells of odontogenic epithelial follicles. (c) Positive cytoblasmic and nuclear immunoreactivity for SOX2 in odontogenic epithelial strands of plexiform type of conventional ameloblastoma. (d)\u003cstrong\u003e \u003c/strong\u003ePlexiform ameloblastoma shows nuclear and cytoblasmic expression of SOX2 in ameloblast like cells and stellate reticulum like cells in odontogenic epithelial strands. (e) Luminal unicystic ameloblastoma with positive nuclear and cytoblasmic immunoractivity of SOX2 in prolifiratic ameloblastomatous epithelium and chronic inflammatory cells. (f) Mural unicystic ameloblastoma with weak positive cytoblasmic expression of SOX2 in prolifiratic ameloblastomatous epithelium (ABC-DAB ×200).\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6248573/v1/5d6f48d9d1df740866bc1402.jpeg"},{"id":81941351,"identity":"748ff2e3-8e13-423f-8a76-a69b1143b4dd","added_by":"auto","created_at":"2025-05-05 07:08:08","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":140936,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePhotomicrographs show: \u003c/strong\u003e(a) Odontogenic keratocyst with hyperchromatic palisaded basal cells and flat epithelial connective tissue interface (H\u0026amp;E ×200). (b) Moderate nuclear expression of SOX2 in basal and parabasal layers of odontogenic keratocyst epithelial lining (ABC-DAB ×200). (c) Odontogenic keratocyst with strong nuclear immunoreactivity for SOX2 in basal and parabasal cells of epithelial lining (ABC-DAB ×200). (d) Strong nuclear immunoreactivity of SOX2 in basal and parabasal cells of epithelial lining in odontogenic keratocyst (ABC-DAB ×200).\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6248573/v1/e1f11502f75cff7b81d322a3.jpeg"},{"id":81941934,"identity":"b3693472-3c27-4dab-8af0-4ae4fa7986e2","added_by":"auto","created_at":"2025-05-05 07:16:08","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":492377,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ephotomicrographs shows \u003c/strong\u003e(a) Dentigerous cyst with thin odontogenic epithelium of 2-4 cell thickness with flat epithelial connective tissue interface (H\u0026amp;E ×200). (b) Dentigerous cyst with weak cytoblasmic expression of SOX2 in epithelial lining (ABC-DAB ×200). (c) Moderate nuclear and cytoblasmic immunoreactivity for SOX2 in Dentigerous cyst epithelial lining (ABC-DAB ×200).\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6248573/v1/339deefee332d0e8619fdcc3.jpeg"},{"id":95040023,"identity":"b44ae5ab-f436-40fd-a8e0-59aca9302ad9","added_by":"auto","created_at":"2025-11-03 16:07:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5373178,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6248573/v1/3bd69e1b-959b-4445-9dcb-aec9a2b1feee.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluation of The Prognostic Role of Sox2 as A Tumor Stem Cell Marker in Odontogenic Cysts and Tumors: Clinical, Radiographic and Immunohistochemical Correlation","fulltext":[{"header":"Background","content":"\u003cp\u003eOdontogenic cysts and tumors are among the most often observed pathological lesions in the head and neck region, which can be defined as clinico-pathological entities with inherent degrees of biological aggressiveness and wide range of disease behavior.\u003csup\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/sup\u003e Considerable variation in the clinicopathologic features can sometimes be challenging and increase the chance of misdiagnosis. The prognosis of these lesions varies depending on their biological behavior, recurrence potential and treatment approach; Some lesions have excellent outcomes when diagnosed early, while others are aggressive and require long term follow up. \u003csup\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAmeloblastoma (Ab) is the most common odontogenic epithelial tumor, accounting for 9\u0026ndash;11% of odontogenic tumors.\u003csup\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/sup\u003e It is represented by slow growth, asymptomatic swelling and/or perforation of the cortical bone and might grow into massive proportions causing facial deformity.\u003csup\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/sup\u003e Although Ab is a benign odontogenic tumor of jawbones, it is characterized by its aggressive local invasion and high recurrence incidence up to 55%-90%, which necessitate precise histological diagnosis and radical surgical treatment. Additionally, few reports of distant metastatic ameloblastomas were documented. \u003csup\u003e(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/sup\u003e The high level of tumor stem cells in Ab may represent a cause for tumor recurrence.\u003csup\u003e(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOdontogenic Keratocyst (OKC) is a distinctive type of odontogenic cysts with an aggressive clinical potential and high recurrence rate (25\u0026ndash;60%).\u003csup\u003e(8)\u003c/sup\u003e It differs from typical cysts in growth pattern and biological behavior, its growth is triggered by the active proliferation of the epithelial lining rather than the osmotic pressure of the cystic fluid. As OKC grows through extension rather than expansion, it develops antero-posteriorly with limited initial indication of cortical expansion. The destructive nature of OKC and recurrence potential has many theories for the cyst to be consider a tumor. \u003csup\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAnother common cyst of non-inflammatory odontogenic origin, is the Dentigerous cyst that arises from the pericoronal tissue of an impacted tooth.\u003csup\u003e(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/sup\u003e Clinically, DCs are often asymptomatic and could be diagnosed incidentally during an oral check-up, but may occasionally cause enormous swelling and dental displacement. Radiographically, they may resemble an OKC or an Ab. DC has good prognosis and rarely recurs, however radiolucencies greater than 4 mm are thought to indicate more aggressive behavior, which can result in tooth displacement. \u003csup\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA set of genetic and molecular alterations are involved in the pathogenesis, progression and clinical behavior of odontogenic lesions. The exact mechanism remains unclear, recent studies suggest that it may be evolved by a stem cell population called the tumor stem cells (TSCs) or cancer stem cells (CSCs).\u003csup\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSOX2 is a characteristic member of the SOX family of transcription factors, which is considered a subpopulation of stemness-related genes. It is essential for early development, maintenance and self-renewal of undifferentiated stem cells. It is evident in embryonic and adult stem cells, and play an essential role in maintaining pluripotency. \u003csup\u003e(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/sup\u003e It has been found to be related to oncogenic signaling pathways, controlling tumor cells by affecting their fate, proliferation and apoptosis. \u003csup\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSOX2 is a principle marker for dental epithelial and mesenchymal stem cells associated with tooth renewal and replacement.\u003csup\u003e(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/sup\u003e Recent studies indicate that sox2 can be a potential novel biomarker to distinguish between malignant, and benign lesions as it is a specific and sensitive marker for high-grade lesions. Furthermore, it has been linked to the process of tumor initiation, destructive clinical course and poor prognosis. \u003csup\u003e(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eVariable SOX2 expression was noted in different types of benign and malignant neoplasms.\u003csup\u003e(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/sup\u003e This has been linked to the stem-like characteristics of tumor cells. Poor patient prognosis was associated with elevated SOX2 expression in cancers of the oral cavity, esophagus, breast, liver, rectal and prostate. \u003csup\u003e(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/sup\u003e Available data in literature suggest that SOX2 is expressed differently in odontogenic cysts and tumors which may reflect their different histogenesis, however, few research correlate SOX2 expression to clinical and radiological findings in benign odontogenic cysts and tumors. Predicting biological behavior and prognosis of these common lesions will greatly aid in patient management and improve treatment outcomes.\u003c/p\u003e \u003cp\u003eIn order to evaluate the prognostic role of the stem cell marker SOX2, and determine whether its expression in Ab, OKC, and DC is associated with the clinico-biological behavior of these lesions, this study aimed to assess the immunoexpression of SOX2 in these tissues and correlate SOX2 immunohistochemical staining score to clinical data, radiographic findings and recurrence ratio.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003eForty-Five patients diagnosed with benign odontogenic cysts or tumors (Ab, OKC and DC) either in maxilla or mandible and needed surgical treatment were selected from the Out-Patient Clinic of Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Mansoura University. No age or gender preference was specified in this study. Histopathological examination and immunohistochemistry (IHC) staining of tissue samples were done at Oral Pathology Department Faculty of Dentistry, Mansoura University.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthics and Consent\u003c/h3\u003e\n\u003cp\u003eAll patients were informed about the aim of the designed study, complete treatment plan and a written consent was obtained. The institutional Review Board (IRB) of the Faculty of Dentistry, Mansoura University, Mansoura, Egypt, approved the current study in compliance with the seventh revision of the Helsinki Declaration in 2013 under protocol number (No. A06010222). It is registered in Clinical-Trials.gov PRS (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://register.clinicaltrials.gov\u003c/span\u003e\u003cspan address=\"https://register.clinicaltrials.gov\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) under identification number NCT06833840 on 01/21/2025.\u003c/p\u003e\n\u003ch3\u003eSample Size Calculation\u003c/h3\u003e\n\u003cp\u003eSample size calculation was based on mean of SOX2 percentage area among ameloblastoma and odontogenic keratocyst obtained from previous research.\u003csup\u003e(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/sup\u003e Using G*power version 3.1.9.4\u003csup\u003e(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/sup\u003e to calculate sample size based on effect size of 1.9333975, 2-tailed test, α error\u0026thinsp;=\u0026thinsp;0.05 and power\u0026thinsp;=\u0026thinsp;95.0% then a sample of 15 cases per group would be required.\u003c/p\u003e\n\u003ch3\u003eStudy Design\u003c/h3\u003e\n\u003cp\u003eThis is a prospective immunohistochemical study through which fifty-five patients with suspected odontogenic cysts or tumors underwent further clinical and radiographic assessment. Incisional or excisional biopsy was carried out according to the lesion size and site, histopathological diagnosis of all tissue specimens to confirm lesion type was done based on 2022 WHO Classification of Head and Neck cysts and tumors.\u003csup\u003e(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAfter exclusion of non-eligible lesions, forty-five specimens were included in this study and were divided into 3 groups:\u003c/p\u003e \u003cp\u003eGroup A: including 15 cases of Ameloblastoma (Ab).\u003c/p\u003e \u003cp\u003eGroup B: including 15 cases of Odontogenic Keratocyst (OKC).\u003c/p\u003e \u003cp\u003eGroup C: including 15 cases of Dentigerous Cyst (DC).\u003c/p\u003e\n\u003ch3\u003eSurgical Procedures\u003c/h3\u003e\n\u003cp\u003eAfter detailed data collection, a complete clinical and radiographic examination (Panoramic x-ray and Cone Beam Computed Tomography) was done for each patient. Lesion site, size, pattern of radiolucency, relation to anatomical landmarks and buccal or lingual cortical bone perforation were assessed.\u003c/p\u003e \u003cp\u003eAn incisional or excisional biopsy was obtained according to the lesion size, the tissue specimens were fixed in 10% neutral formalin and were sent to the Oral Pathology Department, Faculty of Dentistry, Mansoura University where it was preserved into paraffin blocks and histopathologically diagnosed using hematoxylin and eosin staining. According to the diagnosis of each lesion, suitable surgical intervention including marsupialization followed by enucleation, enucleation and curettage, marginal or segmental resection were utilized in the management of different cases in this study.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eImmunohistochemical marker\u003c/h2\u003e \u003cp\u003eRabbit Polyclonal Antibody for Sex-determining region Y (SRY)-box 2(SOX2), BIOCYC Gesellschaft f\u0026uuml;r Biotechnologie, Germany (Catalog No. 2-SO108-13, 7 ml Ready-to-use).\u003c/p\u003e \u003cp\u003e \u003cb\u003eImmunohistochemical staining\u003c/b\u003e \u003csup\u003e(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eSections of 4 \u0026micro; thickness were cut from paraffin blocks, mounted on negatively charged Opti plus slides for assessment of SOX2 using a universal kit (1.0 Poly HRP DAB Kit). After being deparaffinized in xylene, the sections were rehydrated in alcohol at decreasing concentrations. Antigen Retrieval was performed. After 10 minutes of immersion in citrate buffer PH6, the slides were heated, blocked for 30 minutes using 1.5% horse serum from \"Santa Cruz Biotechnology,\" and then diluted in phosphate buffered solution (PBS).\u003c/p\u003e \u003cp\u003eIncubation of primary antibodies of Rabbit Polyclonal Anti-SOX2 at room temperature (45min). Slides were washed with PBS (3 minutes). The slides were then incubated with the secondary antibody for 25 minutes at room temperature then were washed in PBS for 3 minutes. Slides were treated with streptavidin\u0026ndash;biotin enzyme reagent \u0026ldquo;DAKO, Denmark\u0026rdquo; (10 minutes) and rewashed in PBS (3 minutes).\u003c/p\u003e \u003cp\u003eTo create color, drops of \"3.3 Diaminobenzidine tetrahydrochloride\" (DAB) were used as a chromogen. Mayers hematoxylin was used as a counterstain, and sections were fixed for three minutes using a mounting media based on xylene. Positive immune deposits were detected as brown spots. As positive control, Squamous Cell Carcinoma (SCC) was used for confirmation of the marker expression. Negative controls were prepared using non-immune serum.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEvaluation of immunohistochemical staining\u003c/h3\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eSemi-quantitative method for subjectively scoring the immunohistochemical staining\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eImmunohistochemically stained sections were interpreted independently by two pathologists. The immune reactivity for SOX2 was assessed by a scoring system based on the both percentage and intensity of staining.\u003csup\u003e(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/sup\u003e Specimens were considered to be positive for staining when the cells had a brown nucleus.\u003c/p\u003e \u003cp\u003eImmune reactivity was evaluated by scanning the slides under a light microscope at 200x magnification. Five fields were selected that were rich in lesional cells. \u003cb\u003eThe percentage of staining\u003c/b\u003e was graded from (0:4), 0\u0026thinsp;=\u0026thinsp;negative, 1\u0026thinsp;=\u0026thinsp;1:25%, 2\u0026thinsp;=\u0026thinsp;26:50%, 3\u0026thinsp;=\u0026thinsp;51:75, and 4\u0026thinsp;=\u0026thinsp;76:100%. \u003cb\u003eThe intensity\u003c/b\u003e was interpreted from (0:3) as 0\u0026thinsp;=\u0026thinsp;negative, 1\u0026thinsp;=\u0026thinsp;weak, 2\u0026thinsp;=\u0026thinsp;moderate and 3\u0026thinsp;=\u0026thinsp;strong.\u003c/p\u003e \u003cp\u003eThe percentage and intensity scores were then added to obtain \u003cb\u003ea total score\u003c/b\u003e, which ranged from 0 to 7. The cases were categorized into one of the following categories according to their overall scores: Negative expression\u0026thinsp;=\u0026thinsp;0 points, Low expression\u0026thinsp;=\u0026thinsp;1:3 points and High expression\u0026thinsp;=\u0026thinsp;4:7 points.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinical and Radiological correlation\u003c/h2\u003e \u003cp\u003eStatistical correlations of SOX2 immunohistochemical total staining scores to clinical data including patient age, sex and recurrence, and to radiological findings including lesion site, radiographic loculation pattern, root resorption and buccal or lingual cortical bone perforation were analyzed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData was fed to the computer and analyzed using GraphPad Prism 8 (GraphPad Software). Normally distributed data were presented as mean, and standard deviation (SD) values, the One-way ANOVA followed by post hoc Tukey\u0026rsquo;s multiple comparison test were used to compare between them. While non-normally distributed data were presented as median, and range values, the Kruskal-Wallis test followed by post hoc Dunn's multiple comparisons test were used to compare between these groups. Chi-square tests of goodness of fit and independence were used to compare the categorical data groups. Spearman's rank correlation coefficient was used where the value r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;1 means a perfect negative correlation and the value r\u0026thinsp;=\u0026thinsp;1 means a perfect positive one. The significance of the results obtained was judged at the (0.05) level.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eI. Clinical Results:\u003c/h2\u003e \u003cp\u003eAs shown in (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e); The mean patients age of Ab, OKC and DC groups were 33.80\u0026thinsp;\u0026plusmn;\u0026thinsp;14.65, 32.67\u0026thinsp;\u0026plusmn;\u0026thinsp;15.01, and 28.07\u0026thinsp;\u0026plusmn;\u0026thinsp;10.87 years respectively with no statistical significant difference (P\u0026thinsp;=\u0026thinsp;0.48). Twenty-seven patients (60%) were males while eighteen patients (40%) were females. The number of males and females in each group was provided in Table\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, along with the corresponding percentages. Thirty-eight lesions were found in mandible with posterior mandible predominance (6 in anterior mandible and 32 in posterior mandible) while seven lesions were found in maxilla (2 in anterior maxilla and 5 in posterior maxilla). The distribution of number and percentage of lesions sites between groups were shown in (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The results showed no statistically significant difference in the maxillary and mandibular distributions among studied groups (p\u0026thinsp;=\u0026thinsp;0.31). Five patients included in this study were received as recurrent cases, distributed as 3 (20%), 2 (13.3%), 0 (0%) among Ab, OKC and DC groups respectively. The histopathological assessment of recurrent cases of Ab revealed that 2 cases were conventional Ab of follicular histopathological variants, and the third case was unicystic Ab with mural histopathological variant.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical data (patients age, sex, lesion site, patients received as recurrent)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eSite\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003ePatients\u003c/p\u003e \u003cp\u003eReceived as\u003c/p\u003e \u003cp\u003erecurrent\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMaxilla Mandible\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAnt post\u003c/p\u003e \u003cp\u003en (%) n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAnt Post\u003c/p\u003e \u003cp\u003en (%) n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAb\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e10 5\u003c/p\u003e \u003cp\u003e(66.7%) (33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33.80\u0026thinsp;\u0026plusmn;\u0026thinsp;14.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 0\u003c/p\u003e \u003cp\u003e(6.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 10\u003c/p\u003e \u003cp\u003e(26.7%) (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOKC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e9 6\u003c/p\u003e \u003cp\u003e(60%) (40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.67\u0026thinsp;\u0026plusmn;\u0026thinsp;15.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 2\u003c/p\u003e \u003cp\u003e(6.6%) (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 12\u003c/p\u003e \u003cp\u003e(80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(13.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e8 7\u003c/p\u003e \u003cp\u003e(53.3) (46.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.07\u0026thinsp;\u0026plusmn;\u0026thinsp;10.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 3 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 10\u003c/p\u003e \u003cp\u003e(13.3%) (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.556\u003c/p\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u0026thinsp;=\u0026thinsp;0.743\u003c/p\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;7.113\u003c/p\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;3.15\u003c/p\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAb: Ameloblastoma, OKC: Odontogenic keratocyst, DC: Dentigerous cyst, SD: standared deviation, Ant: Anterior, Post: Posterior, n\u0026thinsp;=\u0026thinsp;number of patients, X\u003csup\u003e2\u003c/sup\u003e: chi-square test, F: One way ANOVA, P: not significant (at level p\u0026thinsp;\u0026lt;\u0026thinsp;.05)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eII. Radiographic Results:\u003c/h2\u003e \u003cp\u003e1- Radiographic locular pattern:\u003c/p\u003e \u003cp\u003eAb group had a higher percentage of multilocular radiolucencies (66.7%) compared to the OKC (26.7%) and DC (13.3%) groups. OKC and DS groups had higher percentages of unilocular radiolucencies (73.3% and 86.7%) compared to the Ab (33.3%) group. The results showed a statistically significant difference in locular pattern between the groups (p\u0026thinsp;=\u0026thinsp;0.002*) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRadiographic features\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eLoculation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBone Perforation\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRoot resorption\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnilocular\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMultilocular\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAb\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e5 (33.3%) 10 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOKC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e11 (73.3%) 4 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e13 (86.7%) 2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTest\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e X\u003csup\u003e2\u003c/sup\u003e\u003csub\u003e=\u003c/sub\u003e10.08\u003c/p\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.002*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003csub\u003eX\u003c/sub\u003e X\u003csup\u003e2\u003c/sup\u003e\u003csub\u003e=\u003c/sub\u003e16.12\u003c/p\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.0001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eX\u003csup\u003e2\u003c/sup\u003e\u003csub\u003e=\u003c/sub\u003e8.86\u003c/p\u003e \u003cp\u003eP\u0026thinsp;=\u0026thinsp;0.003*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAb: Ameloblastoma, OKC: Odontogenic keratocyst, DC: Dentigerous cyst\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eX\u003csup\u003e2\u003c/sup\u003e: Chi square test, *Statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e2- Association of bone perforation:\u003c/p\u003e \u003cp\u003eThe Ab group had a higher percentage of cases associated with bone perforation (60%) compared to the OKC (13.3%) and DC groups (0%). The results revealed a significant difference in the association of bone perforation between the groups (p\u0026thinsp;=\u0026thinsp;0.0001*) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e3- Root resorption:\u003c/p\u003e \u003cp\u003eEight cases of Ab, one keratocyst and 3 dentigerous cysts were associated with root resorption in one or more of included teeth. The results revealed a significant difference in the association of root resorption between the groups (p\u0026thinsp;=\u0026thinsp;0.003*) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eIII. Histopathological results\u003c/h2\u003e \u003cp\u003eThe histopathological assessment of Ab revealed 10 cases of conventional Ameloblastoma, which were subdivided into 5 follicular, 3 plexiform, 1 acanthomatous and 1 desmoplastic variants. In addition to 5 cases of unicystic ameloblastoma subdivided into 3 mural, 1 luminal and 1 intraluminal subtypes. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e: a-f).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eHistopathological features by H\u0026amp;E stain for keratocyst and dentigerous cyst were shown in (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003ea) and (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003ea).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eIV. Immunohistochemical results\u003c/h2\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003eSOX2 staining score:\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eAmeloblastoma\u003c/strong\u003e \u003cp\u003eOnly one case showed negative immunoreaction. SOX2 gene expression was observed in fourteen cases of Ab with moderate to strong intensity. By calculating total score, 66.6% (10 cases) recorded high positive scores, 26.7% (4 cases) recorded low positive expression. (median of total score\u0026thinsp;=\u0026thinsp;4) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eSOX2 scores of staining percentage and intensity\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSOX2 staining percentage\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSOX2 intensity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal score\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003escore 0 score1 score2 score3 score4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003escore 1 score2 score 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNegative Low High\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAb\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 4 6 4 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 7 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(6.7%) 4 (26.7%) 10 (66.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOKC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 2 8 5 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 3 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 1 (6.7%) 14 (93.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 10 5 0 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 5 0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 13(86.7%) 2 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.007*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ebetween groups\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eP1\u0026thinsp;=\u0026thinsp;0.264\u003c/p\u003e \u003cp\u003eP2\u0026thinsp;=\u0026thinsp;0.044*\u003c/p\u003e \u003cp\u003eP3\u0026thinsp;=\u0026thinsp;0.002*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP1\u0026thinsp;=\u0026thinsp;0.022*\u003c/p\u003e \u003cp\u003eP2\u0026thinsp;=\u0026thinsp;0.040*\u003c/p\u003e \u003cp\u003eP3\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP1\u0026thinsp;=\u0026thinsp;0.048*\u003c/p\u003e \u003cp\u003eP2\u0026thinsp;=\u0026thinsp;0.012*\u003c/p\u003e \u003cp\u003eP3\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAb: Ameloblastoma, OKC: Odontogenic keratocyst, DC: Dentigerous cyst\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eUsed test: Kruskal-Wallis test followed by post hoc Dunn's multiple comparisons test.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eP1: significance between AB and OKC groups, P2: significance between AB and DC groups, and P3: significance between OKC and DC\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003eThe expression was mainly nuclear in ameloblast like cells at the periphery of ameloblastic units, also large number of cases showed cytoplasmic expression which indicate more tumor aggressiveness. (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e3\u003c/span\u003ea-f).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eOKC\u003c/b\u003e: The SOX2 expression was detected in basal and suprabasal layers of all cases with high positive expression in 14 cases (93.3%) and only one case showed low positive expression (6.7%), (median of total score\u0026thinsp;=\u0026thinsp;5) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e: b-d)\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDC\u003c/strong\u003e \u003cp\u003eWeak to moderate intensity of SOX2 expression was observed in the cytoplasm of basal and supra-basal layers (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003eb-c). By calculating total score, SOX2 expression was low positive in 13 cases (86.7%) and 2 cases recorded high positive expression (13.3%), (median of total score\u0026thinsp;=\u0026thinsp;3) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation of SOX2 IHC staining scores to clinical \u0026amp; radiographic findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrelation with SOX2\u003c/p\u003e \u003cp\u003eIHC staining score\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpearman's rank\u003c/p\u003e \u003cp\u003ecorrelation coefficient (r)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.0242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.874\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.2417\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.162\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRecurrence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.467\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRoot resorption\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2807\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiographic loculation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.137\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBone perforation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.040*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;0.05)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003eStatistical analysis showed significant difference in SOX2 expression between Ab and DC (P\u0026thinsp;=\u0026thinsp;0.012) and between OKC and DC (P\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, OKC recorded a significantly higher SOX2 expression than Ab (P\u0026thinsp;=\u0026thinsp;0.048)\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003eV. Correlation results\u003c/h2\u003e \u003cp\u003eCorrelation of SOX2 IHC staining scores to clinical \u0026amp; radiographic findings revealed a non-statistically significant correlation to age and gender, non-significant positive correlation to root resorption and multilocular radiolucency pattern. While it revealed significant medium positive correlation to bone perforation (P\u0026thinsp;=\u0026thinsp;0.04) and a significant high positive correlation to recurrence (P\u0026thinsp;=\u0026thinsp;0.001). (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eRecent studies suggest that tumor Stem cells play a crucial role in the initiation, progression, aggressiveness and recurrent nature of odontogenic cysts and tumors.\u003csup\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/sup\u003e This study aimed to assess the prognostic role of SOX2 as a tumor stem cell marker in odontogenic cysts and tumors; it is one of the primary studies which correlate SOX2 immunohistochemical staining scores to different clinical and radiological findings in these common pathologies.\u003c/p\u003e \u003cp\u003eThe lesions investigated in this study were ameloblastoma and odontogenic keratocyst, as they possess great clinical interest due to their aggressive biological behavior and tendency to recurrence, and the dentigerous cyst (DC) as it is the most common developmental odontogenic cyst. The expression of stem cell marker was documented via immunohistochemistry as it is considered the gold-standard for the detection of the tissue-specific expression of proteins and their precise subcellular localization. \u003csup\u003e(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn this study, 15 cases of both conventional and unicystic Ab were assessed, follicular form was the most recorded pathological variant followed by Plexiform. SOX2 gene expression was observed in all studied Ab cases except one case of unicystic type. These findings are in accordance with Pagella et al.,2020\u003csup\u003e(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/sup\u003e who reported the widespread expression of the dental epithelial stem cell marker SOX2 within Ameloblastomas, suggested that a major proportion of the cells composing these tumors present Cancer stem cells-like properties and would explain its aggressive behavior.\u003c/p\u003e \u003cp\u003eMost of the included Ab specimens showed moderate to high SOX2 intensity. As regards SOX2 IHC total scores; 10 cases showed high positive scores and 4 cases recorded low positive scores. The expression was mainly nuclear in ameloblast like cells at the periphery of ameloblastic units, but also large number of cases showed nuclear and cytoplasmic expression. According to \u003cb\u003evan Schaijik et al.,2018\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/sup\u003e this cytoplasmic expression of SOX2 could be an indicator of more tumor aggressiveness. Results of this study are in accordance with \u003cb\u003eJurri et al\u003c/b\u003e,\u003csup\u003e(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/sup\u003e who reported that SOX2 was expressed in the epithelial cells of follicular and plexiform ameloblastoma diffusely, suggesting that SOX2 functions in maintaining the progenitor state of epithelium in ameloblastoma.\u003c/p\u003e \u003cp\u003eA statistically significant higher SOX2 expression in Ab than dentigerous cyst was recorded in this study (P\u0026thinsp;=\u0026thinsp;0.012). This result resembles the findings by \u003cb\u003eBalbinot et al., 2023\u003c/b\u003e,\u003csup\u003e(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/sup\u003e as they reported a greater expression of SOX-2 in Ab in relation to the DC lining epithelium and dental follicle (DF) epithelial nests.\u003c/p\u003e \u003cp\u003eOn the other hand, \u003cb\u003ede Freitas Silva et al 2020\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/sup\u003e and \u003cb\u003eBandyopadhyay et al., 2017\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e)\u003c/sup\u003e investigations revealed that SOX2 was not expressed in Ab specimens. \u003cb\u003ePhattarataratip et al., 2021\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/sup\u003e recorded mild to moderate SOX2 expression, limited to the ameloblast like cells in ameloblastoma. The conflicting results in literature regarding SOX2 expression pattern in ameloblastomas are most likely due to using different antibodies. This variable SOX2 expression pattern in ameloblastomas may suggest that additional molecular mechanism could be responsible for the neoplastic characteristics of this specific odontogenic tumor.\u003c/p\u003e \u003cp\u003eAs regards OKC cases in this study, the SOX2 expression was detected in basal and suprabasal layers of all cases with high positive expression in 14 cases and only one case showed low positive expression. This result is in accordance with \u003cb\u003eBandyopadhyay et al., 2017\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e)\u003c/sup\u003e, \u003cb\u003ede Freitas Silva et al., 2020\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/sup\u003e \u003cb\u003eand Pereira et al., 2023\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/sup\u003e in which all cases showed patent SOX2 expression in all layers of OKC.\u003c/p\u003e \u003cp\u003eThroughout the current analysis, the entire thickness of the OKC epithelial lining had SOX2 staining, which may suggest that all cell layers of OKC specimens retain the progenitor characteristics of odontogenic epithelium, displaying a stem cell-like phenotype and ongoing proliferation. According to \u003cb\u003ede Freitas Silva et al\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/sup\u003e this could suggest that OKC displays keratinocyte differentiation, and validate the epithelium's basal and suprabasal layers' OKC cells' capacity for dedifferentiation. High SOX2 expression in OKC as found in our study may explain the high mitotic activity and aggressive nature of the lesion and point to the imbalance between cell growth and cell death in OKC, which could be a sign of neoplastic attitude and the unusually higher recurrence rate of OKCs than other jaw cysts. These findings provide a rationale for the reclassification of this entity as a tumor.\u003c/p\u003e \u003cp\u003eA statistically significant difference in SOX2 expression was found between OKC and Ab (P\u0026thinsp;=\u0026thinsp;0.048), as well as DC (P\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This was similar to \u003cb\u003ede Freitas Silva et al., 2020\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/sup\u003e \u003cb\u003eand Pereira et al., 2023\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/sup\u003e as they recorded that SOX2 immunoreactivity was statically significant in OKC cases compared to Ab cases. \u003cb\u003ePhattarataratip et al., 2021\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/sup\u003e showed that most OKC (86.7%) expressed high SOX2 expression in more than 50% of epithelial cells, significantly higher than ameloblastoma. This difference may be related to their diverse cells of origin or stage of histogenesis.\u003c/p\u003e \u003cp\u003eIn the current study, DC showed low to moderate SOX2 intensity. IHC scores were low in 13 cases of DC, while only two cases were highly positive. This result is similar to \u003cb\u003eBalbinot et al., 2023\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/sup\u003e where all 10 cases of DC showed low positive expression. Furthermore, \u003cb\u003ePhattarataratip et al., 2021\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/sup\u003e recorded minimal to no SOX2 expression in DC cases \u003cb\u003e.\u003c/b\u003e This proves the fact that DC is not aggressive in its biological behavior, as it is generally accepted that DC is developed from the accumulation of fluid between the reduced enamel epithelium and the crown of an unerupted tooth, while OKC is believed to be derived from the remnants of dental lamina.\u003c/p\u003e \u003cp\u003eRegarding clinical correlations, the mean age of included patients in Ab, OKC \u0026amp; DC groups was 33.80\u0026thinsp;\u0026plusmn;\u0026thinsp;14.65, 32.67\u0026thinsp;\u0026plusmn;\u0026thinsp;15.01, and 28.07\u0026thinsp;\u0026plusmn;\u0026thinsp;10.87 respectively. This was in accordance with the globally reported peak of incidence as reported in many studies.\u003csup\u003e(\u003cspan additionalcitationids=\"CR34 CR35\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e)\u003c/sup\u003e Statistically, there was non-significant correlation between IHC scores and patient age (P\u0026thinsp;=\u0026thinsp;0.874). Concerning gender domination, the results of this study displayed that males are more affected than females in all studied groups; Ab, OKC and DC as the percentage of male patients was 66.7%, 60% and 53.3% respectively. This result seems in line with other studies, \u003csup\u003e(\u003cspan additionalcitationids=\"CR38 CR39\" citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e)\u003c/sup\u003e but in contrast with some results in literature \u003csup\u003e(\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e)\u003c/sup\u003e which showed no sex predilection in Ab, OKC and DC. Correlation was not statistically significant between IHC scores and patient gender (P\u0026thinsp;=\u0026thinsp;0.162)\u003c/p\u003e \u003cp\u003eIn the current work, the most affected site in Ab, OKC and DC was posterior mandibular area with percentage 66.7%, 80% and 66.7% respectively. This result is compatible with most of the reported results in the literature.\u003csup\u003e(\u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e)\u003c/sup\u003e This predominance of posterior mandible may be due to its abundant blood supply, which provides tumors with the oxygen and nutrients they need for survival. \u003csup\u003e(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eFive cases were received as recurrent in our study; 3 recurrent cases were Ab, representing 20% of the group. This result is in line with \u003cb\u003eLei et al., 2024\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/sup\u003e and \u003cb\u003eBwambale et al., 2021\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e)\u003c/sup\u003e studies, in which the recurrence rate was 17.2% and 23.2% respectively. However, \u003cb\u003eYang et al., 2017\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e)\u003c/sup\u003e reported a recurrence rates of 9.8%. In association with histopathological patterns, the recurrent cases in this study were more in follicular variant which agrees with \u003cb\u003eGoh et al., 2021\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e)\u003c/sup\u003e \u003cb\u003eand Hresko et al., 2022\u003c/b\u003e.\u003csup\u003e(\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e)\u003c/sup\u003e In contrast, \u003cb\u003eBwambale et al., 2021\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e)\u003c/sup\u003e reported that plexiform pattern had a higher recurrence rate. According to \u003cb\u003eAu et al., 2019\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e)\u003c/sup\u003e, there is no correlation between histological patterns and ameloblastoma recurrence.\u003c/p\u003e \u003cp\u003eAmong OKC group, 2 cases were received as recurrent with percentage 13.3%. This percentage is similar to \u003cb\u003eRahman et al., 2019\u003c/b\u003e.\u003csup\u003e(\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e)\u003c/sup\u003e High recurrence rate may be due to the presence of satellite cysts and the thin cystic epithelium ,which has a lower tensile strength than other maxillofacial tumors, making it challenging to remove the tumor entirely in toto. \u003csup\u003e(\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e)\u003c/sup\u003e Additionally, dedifferentiation of the basal and suprabasal cells in OKC may be the cause of satellite cyst-induced recurrence. \u003csup\u003e(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA significant positive correlation was found between IHC scores and recurrence (P\u0026thinsp;=\u0026thinsp;0.001) as the specimens of recurrent cases showed strong SOX2 overexpression. Similarly, \u003cb\u003eTseng et al., 2022\u003c/b\u003e,\u003csup\u003e(\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e)\u003c/sup\u003e found that recurrent cases of Ab showed much higher labeling indices of SOX2 than paired primary lesions, and proposed that recurrence of Ab is associated with the presence of SOX2-expressing stem cells, as some tumor nests might be remained when the tumor was not adequately removed, SOX2 expressing cells remaining in these nests might give rise to the recurrent disease. \u003cb\u003eVanner et al.\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e)\u003c/sup\u003e showed that the SOX2 cells were quiescent in comparison to other tumor cells that cycled quickly, and that these SOX2 cells cause tumor regrowth following therapy.\u003c/p\u003e \u003cp\u003eRegarding radiographic results, 66.67% of the Ab showed multilocular radiolucency, these results were comparable to the radiographic image reported in \u003cb\u003eSmit et al., 2024\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/sup\u003e and \u003cb\u003eMalik et al., 2018.\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e)\u003c/sup\u003e \u003cb\u003eBoffano et al., 2021\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e)\u003c/sup\u003e mentioned that multilocular radiographic appearance of Ab was associated with high risk of recurrence. In this study, 73.3% of OKC patients and 86.7% of DC cases had clearly defined unilocular radiolucency, which is consistent with findings of \u003cb\u003eRahman et al 2019\u003c/b\u003e,\u003csup\u003e(\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e)\u003c/sup\u003e and \u003cb\u003eTerauchi et al., 2019.\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e)\u003c/sup\u003e However some big cysts exhibit a multilocular picture on panoramic radiographs, which is believed to be caused by the persistence of bone trabeculae within the radiolucency. \u003csup\u003e(\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eNo significant correlation was found between SOX2 expression and the radiographic locular pattern of lesions in this study (P\u0026thinsp;=\u0026thinsp;0.137), as well as root resorption of included teeth (P\u0026thinsp;=\u0026thinsp;0.062).\u003c/p\u003e \u003cp\u003eCurrent study showed cortical bone perforation in 60% of Ab cases in computed tomography x-ray (CBCT) which agrees with \u003cb\u003eSmit et al., 2024\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e)\u003c/sup\u003e who recorded cortical perforation in 77% of cases, this high percent points to the aggressiveness of this lesion. Two cases showed bone perforation in OKC, which demarcated the growth behavior of these lesions as the OKCs develop anteroposteriorly with little initial sign of cortical expansion. \u003csup\u003e(\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e)\u003c/sup\u003e However, other studies reported higher incidence of bone perforation associated with keratocyst (71.4%). \u003csup\u003e(\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA significant correlation was found between SOX2 and cortical bone perforation (P\u0026thinsp;=\u0026thinsp;0.04). This result is in accordance with \u003cb\u003eCarneiro et al\u003c/b\u003e\u003csup\u003e(\u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e)\u003c/sup\u003e, who correlated the imaging aspects of odontogenic cysts and tumors in CBCT to the lesion behavior, and reported that cortical perforation is the most indicative factor of an aggressive behavior. His results similarly to ours showed that aggressive lesions including ameloblastoma and keratocyst were highly associated with cortical bone perforation while among the non-aggressive lesions, the dentigerous cyst was not associated with cortical perforation. \u003cb\u003eFidele et al\u003c/b\u003e \u003csup\u003e(\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e)\u003c/sup\u003e reported that Enucleation of keratocysts combined with cortical perforation was statistically associated with high recurrence rate.\u003c/p\u003e \u003cp\u003eAll these findings which observed a strong positive expression of SOX2 transcription factor in OKC and Ab suggest that these lesions have cells with characteristics of cancer stem cells (CSs) that could be related to the progression and recurrence of these aggressive odontogenic pathologies.\u003c/p\u003e \u003cp\u003eTo sum up, this study showed that SOX2 expression is a valid indicator of the stem cell populations in odontogenic cysts and tumors. These cells have the capacity for self-renewal and pluripotency, which would account for the aggressive nature and recurrence of Abs and OKCs. Additionally, this study recorded correlation of SOX2 expression to cortical bone perforation and recurrence of these lesions which point to the biological behavior of these lesions, clinical outcome and poor prognosis. Predicting the prognosis of such aggressive lesions provides great value in patient management, avoiding recurrence, lowering patient morbidity and improving the treatment outcome.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study clarified the diagnostic and prognostic relevance of SOX2 tumor stem cell marker in odontogenic cysts and tumors. A strong positive expression of SOX2 transcription factor was observed in OKC and Ab, suggesting that these lesions have cells with characteristics of cancer stem cells (CSs) that could be related to the progression and recurrence of these aggressive odontogenic pathologies. Positive correlation of SOX2 expression to cortical bone perforation and recurrence of these lesions points to the aggressive biological behavior, clinical outcome and poor prognosis. Recognizing such factors is of great value to improve treatment outcome of odontogenic lesions. Further studies with a larger study population and more than one marker are recommended.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTSCs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTumor stem cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOX-2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esex-determining region Y (SRY)-box 2\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAb\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAmeloblastomas\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOKC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdontogenic Keratocyst\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDentigerous cyst\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eImmunohistochemical\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOTs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eOdontogenic tumors\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOPG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epanoramic X-ray\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCSCs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCancer stem cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIRB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThe Institutional Review Board\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePBS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ephosphate buffered solution\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDAB\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDiaminobenzidine tetrahydrochloride\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSquamos cell carcinoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003edental follicle\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHaneen Mahmoud Zeen El-Abdeen\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003ePerforming the Surgical Procedures, Formal Analysis, Data Curation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMohamed Abdel-Monem Tawfik\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eConceptualization, Supervision, Project Administration, Approving Final Manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSherif Yousef Elnagdy\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eHistopathological examination and immunohistochemistry of tissue samples,Reviewing and Editing the Final Manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNoha Ahmed Mansour:\u0026nbsp;\u003c/strong\u003eConceptualization, Interpretation of Data, Writing the Original Draft, Approving Final Manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e The corresponding author can provide the data sets utilized and/or analyzed for this study upon reasonable request\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u0026nbsp;\u003c/strong\u003eThe institutional Review Board (IRB) of the Faculty of Dentistry, Mansoura University, Mansoura, Egypt, approved the current study in compliance with the seventh revision of the Helsinki Declaration in 2013 under protocol number (No. A06010222).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent:\u003c/strong\u003e According to the guidelines of Mansoura University institution\u0026rsquo;s ethics committee, each participant signed a written informed consent form for participation in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interests:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflict of interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe authors received no funding for this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBanerjee A, Kamath VV, Sundaram L, Krishnamurthy SSJJOS. 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SN Compr Clin Med. 2022;4(1):13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s42399-021-01102-z\u003c/span\u003e\u003cspan address=\"10.1007/s42399-021-01102-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFidele NB, Yueyu Z, Zhao Y, Tianfu W, Liu J, Sun Y, Liu B. Recurrence of odontogenic keratocysts and possible prognostic factors: Review of 455 patients. Med Oral Patol Oral Cir Bucal. 2019;24(4):e491\u0026ndash;501. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.4317/medoral.22827\u003c/span\u003e\u003cspan address=\"10.4317/medoral.22827\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 31232383; PMCID: PMC6667002.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"SOX2, Odontogenic keratocyst, Ameloblastoma, Dentigerous cyst, Immunohistochemistry","lastPublishedDoi":"10.21203/rs.3.rs-6248573/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6248573/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eOdontogenic cysts and tumors are highly encountered jaw lesions with varying clinical characteristics and disease behavior. Its pathogenesis may involve the existence of tumor stem cells. SOX2 transcription factor is expressed in embryonic and adult stem cells and exerts a potent influence on maintaining pluripotency. SOX2 expressing cells would account for the aggressive nature and recurrence of some odontogenic pathologies. To evaluate the prognostic role of SOX2 stem cell marker in odontogenic cysts and tumors and determine whether its expression is associated with the clinico-biological behavior of these lesions, this study aimed to assess the immunoexpression of the stem cell marker SOX2 in ameloblastoma, odontogenic keratocyst and dentigerous cyst and correlate SOX2 immunohistochemical staining scores to clinical and radiographic findings and recurrence of these lesions.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eForty-Five \u003cb\u003es\u003c/b\u003eurgical specimens were included in this study, 15 ameloblastomas (Ab), 15 odontogenic keratocysts (OKC) and 15 dentigerous cysts (DC). An immunohistochemical (IHC) study using the SOX2 Rabbit Polyclonal Antibody was done to evaluate SOX2 expression. A semi-quantitative method for subjectively scoring percentage and intensity of SOX2 staining was carried out. Statistical correlation to clinical data, radiological findings and recurrence were analyzed.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eNuclear SOX2 expression was strong positive within OKC specimens in both basal and sub-basal layers, followed by Ameloblastoma which showed nuclear and cytoplasmic reaction, while most cases of DC recorded low positive scores. Significant difference in SOX2 (IHC) staining scores was found between (OKC) and (DC) (P\u0026thinsp;=\u0026thinsp;\u0026lt;\u0026thinsp;0.001*), as well as between (Ab) and (DC) (P\u0026thinsp;=\u0026thinsp;0.012*), (OKC) showed a significant higher SOX2 expression than ameloblastoma (P\u0026thinsp;=\u0026thinsp;0.048*). A significant positive correlation was found between SOX2 expression and both cortical bone perforation and recurrence (P\u0026thinsp;=\u0026thinsp;0.040*, 0.001*), while no significant correlation to age, gender, root resorption or radiographic loculation (P\u0026thinsp;=\u0026thinsp;0.874, 0.162, 0.062, 0.137).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSOX2 is a reliable marker for tumor stem cells (TSCs) within benign odontogenic lesions. Positive correlation of SOX2 expression to cortical bone perforation and recurrence of these lesions point to the aggressive biological behavior, clinical outcome and poor prognosis. The prognostic role of SOX2 is of great value to improve treatment of odontogenic lesions.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTrial registration\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis study was registered in ClinicalTrials.gov PRS (https//register.clinicaltrials.gov) under identification number NCT06833840 on 01/21/2025.\u003c/p\u003e","manuscriptTitle":"Evaluation of The Prognostic Role of Sox2 as A Tumor Stem Cell Marker in Odontogenic Cysts and Tumors: Clinical, Radiographic and Immunohistochemical Correlation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-05 07:00:03","doi":"10.21203/rs.3.rs-6248573/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-30T05:12:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-12T23:58:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-09T06:23:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222104722338273224471174815916580921977","date":"2025-04-07T05:18:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"255818408598404087661173589589232476276","date":"2025-04-01T18:32:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-01T14:23:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-01T14:19:25+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-27T07:54:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-26T19:17:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2025-03-26T19:16:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d26ee73f-82db-477b-a2eb-4000fe6c5c56","owner":[],"postedDate":"May 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T16:02:40+00:00","versionOfRecord":{"articleIdentity":"rs-6248573","link":"https://doi.org/10.1186/s12903-025-07065-0","journal":{"identity":"bmc-oral-health","isVorOnly":false,"title":"BMC Oral Health"},"publishedOn":"2025-11-01 15:58:15","publishedOnDateReadable":"November 1st, 2025"},"versionCreatedAt":"2025-05-05 07:00:03","video":"","vorDoi":"10.1186/s12903-025-07065-0","vorDoiUrl":"https://doi.org/10.1186/s12903-025-07065-0","workflowStages":[]},"version":"v1","identity":"rs-6248573","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6248573","identity":"rs-6248573","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}