Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study

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Tumor budding is considered as a marker of many important events in oral carcinoma, including the epithelial-mesenchymal transition, invasion, metastasis, and for further prognosis. Methods A total of 30 clinically and histopathologically diagnosed cases of OSCC were retrieved from the archival of the Department of Oral Pathology and Microbiology. After assessing the sections for the presence of tumor budding (TB), it is further categorized into high-intensity TB and low-intensity TB. Results We found a strong association between lymph node metastasis and histopathological grading in the current study. There was no association between TB and a patient’s survival rate. Conclusions This study emphasizes the significance of tumor budding, its relevance to prognosis, and reproducibility, as well as the significance of its evaluation and incorporation into routine surgical pathology practice in the management of OSCC. As a result, we believe that tumor budding is a crucial factor in determining tumor behavior. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/12-1156/v2", "name": "Prognostic role of tumor budding in oral squamous cell carcinoma:..." } } ] } Home Browse Prognostic role of tumor budding in oral squamous cell carcinoma:... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Kalmegh P, Hande A, Gawande M et al. Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.12688/f1000research.133862.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Revised Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] Padmashri Kalmegh https://orcid.org/0000-0002-2492-1643 1 , Alka Hande https://orcid.org/0000-0002-8576-7897 1 , Madhuri Gawande 1 , Swati Patil 1 , Archana Sonone 1 , Aayushi Pakhale https://orcid.org/0000-0002-0529-3856 1 Padmashri Kalmegh https://orcid.org/0000-0002-2492-1643 1 , Alka Hande https://orcid.org/0000-0002-8576-7897 1 , [...] Madhuri Gawande 1 , Swati Patil 1 , Archana Sonone 1 , Aayushi Pakhale https://orcid.org/0000-0002-0529-3856 1 PUBLISHED 12 Jun 2024 Author details Author details 1 Department of Oral & Maxillofacial Pathology and Microbiology, Sharad Pawar Dental College & Hospital, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, Maharashtra, 442004, India Padmashri Kalmegh Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Alka Hande Roles: Data Curation, Investigation, Writing – Review & Editing Madhuri Gawande Roles: Formal Analysis, Software, Writing – Review & Editing Swati Patil Roles: Data Curation, Methodology, Writing – Review & Editing Archana Sonone Roles: Formal Analysis, Visualization, Writing – Review & Editing Aayushi Pakhale Roles: Investigation, Project Administration, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Oncology gateway. This article is included in the Datta Meghe Institute of Higher Education and Research collection. Abstract Background Tumor budding is defined as a single cell or a cluster of up to five tumor cells at the invasion front of all oral squamous cell carcinoma (OSCC) cases. Tumor budding is considered as a marker of many important events in oral carcinoma, including the epithelial-mesenchymal transition, invasion, metastasis, and for further prognosis. Methods A total of 30 clinically and histopathologically diagnosed cases of OSCC were retrieved from the archival of the Department of Oral Pathology and Microbiology. After assessing the sections for the presence of tumor budding (TB), it is further categorized into high-intensity TB and low-intensity TB. Results We found a strong association between lymph node metastasis and histopathological grading in the current study. There was no association between TB and a patient’s survival rate. Conclusions This study emphasizes the significance of tumor budding, its relevance to prognosis, and reproducibility, as well as the significance of its evaluation and incorporation into routine surgical pathology practice in the management of OSCC. As a result, we believe that tumor budding is a crucial factor in determining tumor behavior. READ ALL READ LESS Keywords Epithelial-mesenchymal transition, Histopathological marker, Histological evaluation, Invasive tumor front, Lymph node metastases, Oral squamous cell carcinoma, Prognosis, Tumor budding Corresponding Author(s) Padmashri Kalmegh ( [email protected] ) Close Corresponding author: Padmashri Kalmegh Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2024 Kalmegh P et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Kalmegh P, Hande A, Gawande M et al. Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.12688/f1000research.133862.2 ) First published: 15 Sep 2023, 12 :1156 ( https://doi.org/10.12688/f1000research.133862.1 ) Latest published: 12 Jun 2024, 12 :1156 ( https://doi.org/10.12688/f1000research.133862.2 ) Revised Amendments from Version 1 In the abstract, there was a repetition of the words - lymph node metastasis, removed in the new version. In the histological features, images are replaced and correlated with grading parameters that are - High-intensity tumor buds are >5 clusters of tumor cells and Low-intensity tumor buds are <5 clusters of tumor cells. In the abstract, there was a repetition of the words - lymph node metastasis, removed in the new version. In the histological features, images are replaced and correlated with grading parameters that are - High-intensity tumor buds are >5 clusters of tumor cells and Low-intensity tumor buds are <5 clusters of tumor cells. To read any peer review reports and author responses for this article, follow the "read" links in the Open Peer Review table. READ REVIEWER RESPONSES Introduction In India, oral cancer contributes to two-thirds of cancer cases. Oral squamous cell carcinoma (OSCC) has been categorized as the third most common malignancy and is considered a major risk factor because of increased consumption of tobacco and areca nut. 1 OSCC has a low survival rate due to an early tendency to metastasize and recurrent recurrences. Therefore, early detection, correct diagnosis, and timely treatment are necessary to reduce morbidity and mortality. The invasive tumor front is the region where the most advanced layers of tumor reside, this gives the detailed prognosis of OSCC cases. 2 OSCC cases are usually managed by surgery followed by postoperative radiation therapy. Although diagnostic techniques and treatment methods have improved, the mortality rates of patients with OSCC are still inadequately low with a poor survival rate of five years, challenging the current approaches of prognostic assessment. The aggressive clinical history of OSCC, which includes frequent locoregional relapses and lymph node metastasis (LNM) in more than 60% of cases, makes the prognosis uncertain. 3 , 4 Tumor budding (TB) is the gold standard and reliable histomorphological parameter that has been studied in many cancers. TB is characterized by a dispersed invasive pattern in which epithelial tumor cells are visible at the invasive front as small clusters (up to five cells) spread throughout the stroma at different distances. 5 In the 1950s, Imai et al. , 6 originally described TB as “sprouting”, Gabbert et al. , 7 termed this feature as “tumor dedifferentiation”. Later Morodomi et al. , 8 and Hase et al. , 9 coined the term “budding” as they observed the budding of undifferentiated cells and nests from larger tumor islands. 1 TB is thought to represent the epithelial-mesenchymal transition (EMT), i.e. , the important mechanism for the progression of epithelial cancers. 10 As a result, we aimed to evaluate the importance of TB in the prognosis of OSCC in the current study. Aim This study aimed to perform an evaluation of TB, determine its association with various histopathological parameters, and thereby the prognosis in OSCC. Objectives The objectives of this study were as follows: i) to assess TB in OSCC; ii) to evaluate TNM staging in OSCC; iii) to determine the association between TB with LNM in OSCC; iv) to determine the association between TB and the five year survival rate in OSCC; and v) to determine the association between TB with histopathological grade. Methods The procedure that is employed the most frequently is the manual assessment of TB on hematoxylin and eosin (H&E) stained slides. For the classification of TB intensity, several authors have proposed a variety of techniques with a range of criteria. However, the technique by Wang et al. , 5 from 2011, is one that is the most frequently acknowledged and used in OSCC. According to this approach, TB refers to isolated single cells or clusters of five tumor cells found at the invasive front. To locate the fields with the highest density of TB, a section is initially scanned at low power. Following this, the tumor buds are counted in a single field at a resolution of ×200 or ×20 objective. The samples are then divided into two groups: high-intensity TB (five or more buds) and low-intensity TB (five buds or fewer) or absence TB. Each section in the present study was reviewed by three observers, then by consensus to remove bias. The cases underwent follow-ups at intervals of two months. This study followed the STROBE guidelines. 11 Study setting Daniel formula for sample size estimation: n = Z 2 ∗ P ∗ 1 − P / d 2 Where, Z 2 - The level of significance at 5% i.e. 95% confidence interval =1.96 P = Prevalence of OSCC in India = 80% = 0.80 d = Desired error of margin = 10% = 0.10 n = 1.96 2 ∗ 0.80 ∗ 1 − 0.90 0.10 2 = 30.72 = 30 patients needed in the study Formula Reference: Daniel et al. 12 The present study was conducted from November 2022 at the Department of Oral Pathology and Microbiology, Sharad Pawar Dental College and Hospital, after receiving approval (dated, 05/10/2022) from the Institutional Ethical Committee [DMIMS (DU)/IEC/2022/292] of Datta Meghe Institute of Higher Education and Research, Sawangi (M), Wardha, Maharashtra, India. A total of 30 surgically operated cases of OSCC from the year 2010-2015 at this institute were retrieved from the archival of the department. There were 21 cases that had evaluated TB in OSCC, which included eight cases of well-differentiated squamous cell carcinoma (WDSCC), 12 cases of moderately differentiated squamous cell carcinoma (MDSCC), and one case of poorly differentiated squamous cell carcinoma (PDSCC) with their average age between 30-70 years. In order to assess the survival data, we had telephone conversations with patients or with their relatives. Informed written and verbal consent was taken from all participants involved in the study. Inclusion and exclusion criteria The histopathologically diagnosed and surgically operated cases of OSCC with various histopathological grades were retrieved from the departmental archives. The staging of the patients has been done according to the “American Joint Committee of Cancer” (AJCC) staging system. 13 The cases who had undergone presurgical radiotherapy or chemotherapy, history of second primary or local and distant recurrence, and patients with any other systemic diseases and with coexisting malignancy were excluded from the study. The detailed information of the study population, including the clinical staging of the disease, comprehensive history of pertinent habits with their duration, and histopathological features such as grades of OSCC and lymph node metastasis had been noted. Statistical analysis A chi-squared test was used to test the possible relationship between various clinicopathological variables. The statistical analysis was conducted using IBM SPSS Statistics (RRID: SCR_016479) v27.0 software, and p<0.05 is thought to be the threshold of significance. A chi-squared test, descriptive statistics, and inferential statistics were all used. Results Each clinical and histological feature and TB are cross-tabulated sequentially. Stromal TB was seen in each of the 21 cases. Nine out of the 21 cases (less than five tumor buds) had low-intensity TB, while 11 had high-intensity TB (more than five tumor buds) ( Table 1 ). 25 Out of 30 patients in the current study, 20 cases demonstrated an association between TB and lymph node metastases, while the other 10 cases did not ( Table 2 ). We discovered that out of 20 cases that showed the presence of TB, 12 patients are dead and eight are alive, indicating that there is no connection between TB status and the likelihood of a patient surviving ( Table 3 ). When compared to cases of WDSCC and PDSCC, cases of MDSCC demonstrated the presence of TB ( Table 4 ). This finding suggests that TB can be used as a reliable histopathological parameter for early detection and diagnosis and to determine the prognosis of OSCC cases. Table 1. Evaluation of TB into HI/LI category. TB HI/LI Total χ 2 -value HI LI No findings Present, n (%) 11 (55%) 9 (45%) 0 (0%) 20 (66.67%) 25.95 P=0.0001, S Absent, n (%) 0 (0%) 1 (10%) 9 (90%) 10 (33.33%) Total, n (%) 11 (36.67%) 10 (33.33%) 9 (30%) 30 (100%) Table 2. Association between TB and LNM. TB LNM Total χ 2 -value Yes No Present, n (%) 11 (55%) 9 (45%) 20 (66.67%) 8.68 P=0.003, S Absent, n (%) 0 (0%) 10 (100%) 10 (33.33%) Total, n (%) 11 (36.67%) 19 (63.33%) 30 (100%) Table 3. Association between TB and survival. TB Survival Total χ 2 -value Dead Alive Present, n (%) 8 (40%) 12 (60%) 20 (66.67%) 0.28 P=0.59, NS Absent, n (%) 3 (30%) 7 (70%) 10 (33.33%) Total, n (%) 11 (36.67%) 19 (63.33%) 30 (100%) Table 4. Association between TB and histopathological grading. TB Histopathological grading Total χ 2 -value WDSCC MDSCC PDSCC Present, n (%) 3 (15%) 16 (80%) 1 (5%) 20 (66.67%) 4.19 P=0.040,S Absent, n (%) 5 (50%) 5 (50%) 0 (0%) 10 (33.33%) Total, n (%) 8 (26.67%) 21 (70%) 1 (3.33%) 30 (100%) Histological features The H&E stained section of OSCC shows the presence of TB as indicated by the presence of cell nests containing single-cell infiltration. The invasive front of OSCC is shown by a histological investigation to have tumor buds that are spreading into the underlying connective tissue. High-intensity TB is the presence of >5 cell clusters at the invasive tumor front of the lesion ( Figure 1 , marked by black arrow), and low-intensity TB is the presence of <5 cell clusters at the invasive tumor front of the lesion ( Figure 2 , marked by black arrow). Figure 1. High intensity TB. Under high power view (magnification, ×40). TB, tumor budding. Figure 2. Low intensity TB. Under low power view (magnification, ×10). TB, tumor budding. Discussion OSCC contributes to 95% of oral cancers and predominantly metastasizes to the lymph nodes of the neck. Metastasis of cancer cells to lymph nodes i.e. , positive lymph nodes (LN) is an important adverse prognostic factor for the survival of OSCC cases. 14 In several studies of OSCC, TB has been recorded. Some of these studies have shown that TB is an important prognosticator of LNM, distant metastatic disease and local recurrence. 15 – 18 Strong evidence linking TB and LNM has been established, and multivariate analysis shows that TB is associated with aggressive tumor activity and a bad prognosis in instances, suggesting that TB count can be used to gauge the risk of LNM. 1 , 19 TB count does not require the use of any other expensive techniques or equipment because it is a simple procedure used on a daily basis with the help of H&E stained sections. 15 , 20 TB is not a static histological feature, but it is a series of various processes occurring in an aggressive tumor with the potential to disseminate and metastasize. This biological phenomenon is a dynamic process carried out by a tumor with the potential to invade other tissues, spread and metastasize. 16 TB might be a sign of cells going through EMT, a process in which highly polarized epithelial cells become mobile mesenchymal cells. Therefore, EMT can be regarded as an indicating factor for invasion and subsequent metastasis. 21 Metastasis can be evaluated from the increased distance of the tumor bud and reduced tumor bud size. Significantly more metastases were linked to decreased tumor bud size and increased tumor bud distance. The extent of EMT increased with the distance the tumor buds progressed. Thus, EMT has been related to poor prognostic outcomes in OSCC. 22 Treatment plans and prognosis could be enhanced with precise histological grading and scoring of particular features. Sundar et al. , 23 evaluated the prognostic value of TB in OSCC in 2019. They evaluated TB at the invasive tumor front in all OSCC cases. They discovered that advanced malignancies with tumor sizes larger than 4 cm exhibited high-intensity TB. They came to the conclusion that TB always manifested as an invasive front with cell infiltration in cords or groups. The fact that TB occurs before lymph node metastasis suggests that it is a reliable prognostic marker. They found a significant relationship between LNM and TB. Their research highlighted the significance of TB in the treatment of OSCC cases. 23 The worst pattern of invasion (WPOI) and TB were two histological markers that were evaluated by Chatterjee et al. , in 2019. 17 The risk of LNM, recurrence, and death in early-stage OSCC were found to be best predicted by early detection of these characteristics. The treatment plan and outlook for OSCC are based on the tumor stage and LNM status. During the course of four and a half years, they examined the histological characteristics in 126 samples, including the histological grade, WPOI, TB, lymphovascular emboli, perineural invasion, depth of invasion, and host lymphocyte response. The findings of the study resulted in the recommendation that WPOI and TB be included in the guidelines for histopathological reporting as important risk factors for predicting LNM in all stages of OSCC and reliable prognostic markers. 17 Almangush et al. (2014), 15 investigated the effect of TB on prognosis in OSCC. They examined 16 studies to test this in a meta-analysis. For a better prognosis, they advised using the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) criterion in histology reporting. They assessed the prognostic significance of TB in OSCC. Their research demonstrated a link between lymph node metastasis and TB. TB, which can be seen easily, is a valid prognostic indicator for OSCC and may help with individualized treatment, according to their findings. 15 When compared to lymph nodes without metastasis, TB is significantly (P=0.003) associated with the presence of lymph node metastasis in our study ( Tables 1 and 2 ), which is in accordance with previous studies by Sundar et al. (2019), 23 Chatterjee et al. (2019), 17 Almangush et al. (2014). 15 TB was examined by Joshi et al. (2020), 16 as a potential predictive histopathological feature in oral squamous cell carcinoma. Overall, 30 OSCC cases from January 2018 to August 2019 were investigated. While analyzing invasive tumors, they considered both high-intensity tumor bud clusters of cancer cells and low-intensity tumor bud clusters of cancer cells. There found no evidence of a significant relationship between TB and the survival rate. 16 Candanedo-Gonzalez et al. (2020), 18 investigated incidences of OSCC in the tongue (TSCC), which had a susceptibility to early local spread and recurrence. They reported that TSCC at an early stage (T1/T2N0M0) is not necessarily associated with a favorable prognosis. It is essential to identify prognostic indicators that can be assessed using biopsies. They identified that the EMT, specifically in TSCC, is histologically represented by TB. As a result, they determined that TB in the TSCC was a biological marker that predicted a poor prognosis. 18 The findings of our study (P = 0.59, not significant) ( Table 3 ), demonstrated that there is no relationship between the presence or absence of TB and patient survival rates, which is in accordance with previous studies by Joshi et al. (2020) 16 and Fernando Candanedo-Gonzalez et al. (2020). 18 Nandita et al. (2016), 24 investigated the contribution of TB to the diagnosis of OSCC. For this investigation, 30 histological samples of OSCC with a biopsy-proven diagnosis were chosen. They found tumor cells at the invasive front of the tumor. The number of tumor buds in which TB intensity was at its highest in the histological fields is counted. They used an independent t-test to compare prognostic variables with TB. As a result, they came to the conclusion that the relationship between TB and poor tumor differentiation, as well as its presence, could be crucial indicators to forecast the prognosis of patients with OSCC. 22 Our research is consistent with that of Nandita et al. (2016). 24 In the current study, we came to the conclusion that tumor buds are present in WDSCC and MDSCC at the invasive tumor front as compared to PDSCC ( Table 4 ), suggesting the relevance of TB in early diagnosis of oral squamous cell carcinoma after assessing the existence of TB in various histological grading. Limitations The study is limited by a small sample size, a relatively short follow-up period, and a small number of patients with available follow-up information. Interpretations TB assessment serves as a potential histopathologic prognostic parameter in OSCC. Conclusions To conclude, tumour budding is an essential factor for determining the behaviour of tumours. TB refers to clusters of neoplastic cells at the invasive tumour front than the neoplastic cells in the primary tumour mass. TB is a frequent, repeatable, and easy-to-identify histological factor in OSCC. This study highlights the relevance of TB in prognosis as well as the significance of its evaluation and integration into the routine management of OSCC. Data availability Underlying data Figshare: Short study data- Padmashri.csv. https://doi.org/10.6084/m9.figshare.22778228 . 25 Reporting guidelines Zenodo: STROBE checklist for ‘Prognostic role of tumor budding in oral squamous cell carcinoma’. https://doi.org/10.5281/zenodo.7894541 . 11 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgments We acknowledge the support of laboratory technicians from “Department of Oral & Maxillofacial Pathology and Microbiology”, “Sharad Pawar Dental College & Hospital”, “Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha”. References 1. Kale AD, Angadi PV: Tumor budding is a potential histopathological marker in the prognosis of oral squamous cell carcinoma: Current status and future prospects. J. Oral Maxillofac. Pathol. 2019 Sep; 23 (3): 318. Publisher Full Text 2. Angadi PV, Patil PV, Hallikeri K, et al. : Tumor budding is an independent prognostic factor for prediction of lymph node metastasis in oral squamous cell carcinoma. Int. J. Surg. Pathol. 2015 Apr; 23 (2): 102–110. PubMed Abstract | Publisher Full Text 3. Warnakulasuriya S: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009 Apr 1; 45 (4-5): 309–316. Publisher Full Text 4. Massano J, Regateiro FS, Januário G, et al. : Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2006 Jul 1; 102 (1): 67–76. Publisher Full Text 5. Wang C, Huang H, Huang Z, et al. : Tumor budding correlates with poor prognosis and epithelial-mesenchymal transition in tongue squamous cell carcinoma. J. Oral Pathol. Med. 2011 Aug; 40 (7): 545–551. PubMed Abstract | Publisher Full Text | Free Full Text 6. Imai T: The growth of human carcinoma: a morph anal. Fukuoka Igaku Zasshi. 1954; 45 : 72–102. 7. Gabbert H, Wagner R, Moll R, et al. : Tumor dedifferentiation: an important step in tumor invasion. Clin. Exp. Metastasis. 1985 Oct; 3 : 257–279. PubMed Abstract | Publisher Full Text 8. Morodomi T, Isomoto H, Shirouzu K, et al. : An index for estimating the probability of lymph node metastasis in rectal cancers. Lymph node metastasis and the histopathology of actively invasive regions of cancer. Cancer. 1989 Feb 1; 63 (3): 539–543. PubMed Abstract | <a target="xrefwindow" id="d384205e1131" href="https://doi.org/10.1002/1097-0142(19890201)63:3 Publisher Full Text 9. Hase K, Shatney C, Johnson D, et al. : Prognostic value of tumor “budding” in patients with colorectal cancer. Dis. Colon Rectum. 1993 Jul; 36 : 627–635. Publisher Full Text 10. Dawson H, Lugli A: Molecular and pathogenetic aspects of tumor budding in colorectal cancer. Front. Med. 2015 Mar 10; 2 : 11. Publisher Full Text 11. Kalmegh P: PROGNOSTIC ROLE OF TUMOR BUDDING IN ORAL SQUAMOUS CELL CARCINOMA (Version v1). [Dataset]. Zenodo. 2023. Publisher Full Text 12. Daniel WW, Cross CL: Biostatistics: a foundation for analysis in the health sciences. Wiley; 2018 Nov 13. 13. Byrd DR, Brookland RK, Washington MK, et al. : AJCC cancer staging manual. Amin MB, Edge SB, Greene FL, editors. New York: springer; 2017 Jan. 14. Norling R, Buron BM, Therkildsen MH, et al. : Staging of cervical lymph nodes in oral squamous cell carcinoma: adding ultrasound in clinically lymph node negative patients may improve diagnostic work-up. PLoS One. 2014 Mar 20; 9 (3): e90360. PubMed Abstract | Publisher Full Text | Free Full Text 15. Almangush A, Salo T, Hagström J, et al. : Tumour budding in head and neck squamous cell carcinoma–a systematic review. Histopathology. 2014 Nov; 65 (5): 587–594. PubMed Abstract | Publisher Full Text 16. Joshi P, Pol J, Chougule M, et al. : Tumor budding–A promising prognostic histopathological parameter in oral squamous cell carcinoma–A comparative immunohistochemical study. J. Oral Maxillofac. Pathol. 2020 Sep; 24 (3): 587. PubMed Abstract | Publisher Full Text | Free Full Text 17. Chatterjee D, Bansal V, Malik V, et al. : Tumor budding and worse pattern of invasion can predict nodal metastasis in oral cancers and associated with poor survival in early-stage tumors. Ear Nose Throat J. 2019 Aug; 98 (7): E112–E119. PubMed Abstract | Publisher Full Text 18. Candanedo-Gonzalez F, Antonio OE, De JD: Tumor Budding in Oral Cavity Cancer. Breast Cancer. 2020; 5 (1): 5–23. 19. Ho YY, Wu TY, Cheng HC, et al. : The significance of tumor budding in oral cancer survival and its relevance to the eighth edition of the American Joint Committee on Cancer staging system. Head Neck. 2019 Sep; 41 (9): 2991–3001. PubMed Abstract | Publisher Full Text 20. Grigore AD, Jolly MK, Jia D, et al. : Tumor budding: the name is EMT. Partial EMT. J. Clin. Med. 2016 Apr 29; 5 (5): 51. Publisher Full Text 21. Chang JY, Wright JM, Svoboda KK: Signal transduction pathways involved in epithelial-mesenchymal transition in oral cancer compared with other cancers. Cells Tissues Organs. 2007; 185 (1-3): 40–47. PubMed Abstract | Publisher Full Text 22. Krisanaprakornkit S, Iamaroon A: Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma. ISRN Oncol. 2012 Mar 29; 2012 : 1–10. Publisher Full Text 23. Sundar S: Prognostic value of tumor budding in oral squamous cell carcinoma. Eur. J. Mol. Clin. Med. 2019; 6 (01): 2019. 24. Nandita KP, Boaz K, Srikant N, et al. : Tumour budding: A promising parameter in oral squamous cell carcinoma. Res. J. Pharm., Biol. Chem. Sci. 2016 Sep 1; 7 (5): 2059–2063. 25. Kalmegh P: Short study data- Padmashri.csv. [Dataset]. figshare. 2023. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 15 Sep 2023 ADD YOUR COMMENT Comment Author details Author details 1 Department of Oral & Maxillofacial Pathology and Microbiology, Sharad Pawar Dental College & Hospital, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, Maharashtra, 442004, India Padmashri Kalmegh Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Alka Hande Roles: Data Curation, Investigation, Writing – Review & Editing Madhuri Gawande Roles: Formal Analysis, Software, Writing – Review & Editing Swati Patil Roles: Data Curation, Methodology, Writing – Review & Editing Archana Sonone Roles: Formal Analysis, Visualization, Writing – Review & Editing Aayushi Pakhale Roles: Investigation, Project Administration, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 12 Jun 2024, 12:1156 https://doi.org/10.12688/f1000research.133862.2 version 1 Published: 15 Sep 2023, 12:1156 https://doi.org/10.12688/f1000research.133862.1 Copyright © 2024 Kalmegh P et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Kalmegh P, Hande A, Gawande M et al. Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.12688/f1000research.133862.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 12 Jun 2024 Revised Views 0 Cite How to cite this report: Palve D. Reviewer Report For: Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.5256/f1000research.167793.r290389 ) The direct URL for this report is: https://f1000research.com/articles/12-1156/v2#referee-response-290389 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Jun 2024 Devendra Palve , Oral Pathology & Microbiology, ESIC Dental College & Hospital, Gulgarga, Kalaburagi, Karnataka, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.167793.r290389 No ... Continue reading READ ALL No further comments. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Oral malignancies, Forensic Odontology, Odontogenic tumours I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Palve D. Reviewer Report For: Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.5256/f1000research.167793.r290389 ) The direct URL for this report is: https://f1000research.com/articles/12-1156/v2#referee-response-290389 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 15 Sep 2023 Views 0 Cite How to cite this report: Palve D. Reviewer Report For: Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.5256/f1000research.146877.r248117 ) The direct URL for this report is: https://f1000research.com/articles/12-1156/v1#referee-response-248117 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 Jun 2024 Devendra Palve , Oral Pathology & Microbiology, ESIC Dental College & Hospital, Gulgarga, Kalaburagi, Karnataka, India Approved VIEWS 0 https://doi.org/10.5256/f1000research.146877.r248117 The article stresses on the tumour budding as a marker for prognosis in Oral Squamous cell carcinoma and checking its correlation with lymph node metastasis, TNM staging and five year survival rate. The authors have clearly presented their work that ... Continue reading READ ALL The article stresses on the tumour budding as a marker for prognosis in Oral Squamous cell carcinoma and checking its correlation with lymph node metastasis, TNM staging and five year survival rate. The authors have clearly presented their work that can be accessed online as well. The results have been mentioned clearly along with the statistical results. However, following parts of the article need corrections 1. In the Abstract- Result- " We found a strong association between lymph node metastasis, lymph node metastasis, and histopathological grading in the current study." The message is unclear with repetition of words "lymph node metastasis". 2. In Methods: "high-intensity TB (five or more buds) and low-intensity TB (five buds or fewer)" is not matching with grading shown under Histologic features "High-intensity TB is the presence of >5 cell clusters and low-intensity TB is the presence of <5 cell clusters." The text is to be modified with correct parameters. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Oral malignancies, Forensic Odontology, Odontogenic tumours I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Palve D. Reviewer Report For: Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.5256/f1000research.146877.r248117 ) The direct URL for this report is: https://f1000research.com/articles/12-1156/v1#referee-response-248117 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 15 Sep 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 Version 2 (revision) 12 Jun 24 read Version 1 15 Sep 23 read Devendra Palve , ESIC Dental College & Hospital, Gulgarga, Kalaburagi, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Palve D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 Jun 2024 | for Version 2 Devendra Palve , Oral Pathology & Microbiology, ESIC Dental College & Hospital, Gulgarga, Kalaburagi, Karnataka, India 0 Views copyright © 2024 Palve D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions No further comments. Competing Interests No competing interests were disclosed. Reviewer Expertise Oral malignancies, Forensic Odontology, Odontogenic tumours I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Palve D. Peer Review Report For: Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.5256/f1000research.167793.r290389) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1156/v2#referee-response-290389 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Palve D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 Jun 2024 | for Version 1 Devendra Palve , Oral Pathology & Microbiology, ESIC Dental College & Hospital, Gulgarga, Kalaburagi, Karnataka, India 0 Views copyright © 2024 Palve D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The article stresses on the tumour budding as a marker for prognosis in Oral Squamous cell carcinoma and checking its correlation with lymph node metastasis, TNM staging and five year survival rate. The authors have clearly presented their work that can be accessed online as well. The results have been mentioned clearly along with the statistical results. However, following parts of the article need corrections 1. In the Abstract- Result- " We found a strong association between lymph node metastasis, lymph node metastasis, and histopathological grading in the current study." The message is unclear with repetition of words "lymph node metastasis". 2. In Methods: "high-intensity TB (five or more buds) and low-intensity TB (five buds or fewer)" is not matching with grading shown under Histologic features "High-intensity TB is the presence of >5 cell clusters and low-intensity TB is the presence of <5 cell clusters." The text is to be modified with correct parameters. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Oral malignancies, Forensic Odontology, Odontogenic tumours I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Palve D. Peer Review Report For: Prognostic role of tumor budding in oral squamous cell carcinoma: a retrospective study [version 2; peer review: 1 approved] . F1000Research 2024, 12 :1156 ( https://doi.org/10.5256/f1000research.146877.r248117) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1156/v1#referee-response-248117 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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