Immunohistochemical Expression of Survivin in Colorectal Adenomas and Its Correlation With Grade of Dysplasia - a Cross Sectional Study in a Tertiary Care Centre in South Kerala

Immunohistochemical Expression of Survivin in Colorectal Adenomas and Its Correlation With Grade of Dysplasia - a Cross Sectional Study in a Tertiary Care Centre in South Kerala | 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 Immunohistochemical Expression of Survivin in Colorectal Adenomas and Its Correlation With Grade of Dysplasia - a Cross Sectional Study in a Tertiary Care Centre in South Kerala Dr Shemeera Saidalavi Vellolipadikkal, Dr Lillykutty Pothen, Dr Jessy MM This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9060109/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background Colorectal cancer commonly develops through the adenoma–carcinoma sequence. Survivin, a member of the inhibitor of apoptosis protein family, regulates apoptosis and cell proliferation and is minimally expressed in normal adult tissues. Its re-expression in colorectal neoplasia suggests a role in early tumorigenesis and progression. Objectives To evaluate the immunohistochemical expression of Survivin in colorectal adenomas and to assess its association with the grade of dysplasia. Materials and Methods This cross-sectional study included 40 cases of colorectal adenomas selected by consecutive sampling after ethical clearance. Clinicopathological details were recorded. Histomorphological assessment was performed, followed by immunohistochemical evaluation of Survivin expression. The expression pattern was analysed and correlated with the grade of dysplasia. Results Survivin expression was detected in a significant proportion of colorectal adenomas. A statistically significant increase in Survivin expression was observed with increasing grades of dysplasia, with higher expression noted in high-grade dysplasia compared to low-grade dysplasia. Conclusion Survivin expression shows a significant association with increasing grades of dysplasia in colorectal adenomas, supporting its role in early colorectal tumorigenesis. Immunohistochemical assessment of Survivin may help identify adenomas with higher malignant potential. Colorectal adenoma dysplasia immunohistochemistry Survivin Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Colorectal cancer is one of the most common malignancies worldwide and commonly arises through the well-established adenoma–carcinoma sequence.[ 1 , 2 , 3 ] The risk of malignant transformation increases with advancing grades of dysplasia in colorectal adenomas, highlighting the importance of identifying biomarkers that reflect early neoplastic progression.[ 4 , 5 , 6 ] Survivin, the smallest member of the inhibitor of apoptosis protein family, plays a dual role in regulating apoptosis and cell proliferation. While Survivin expression is prominent during embryonic development, it is largely absent in normal adult tissues. Its re-expression has been demonstrated in a variety of human malignancies, including colorectal neoplasia, suggesting a role in tumor initiation and progression.[ 7 , 8 , 9 ] Several studies have shown increased Survivin expression in colorectal neoplasms, with higher expression reported in lesions showing advanced dysplasia. This supports the hypothesis that Survivin contributes to the adenoma–carcinoma sequence by promoting cell survival and resistance to apoptosis during early tumorigenesis. The present study aims to evaluate the immunohistochemical expression of Survivin in colorectal adenomas and to assess its association with the grade of dysplasia, thereby exploring its potential role as a marker of neoplastic progression in colorectal adenomas. MATERIALS AND METHODS Study Design This was a cross-sectional observational study conducted in the Department of Pathology, Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, over a period of 18 months following approval from the Institutional Ethics Committee. Sample Size Sample size was calculated based on a previous study by Lin et al., which reported Survivin positivity in 31.7% of colorectal adenomas. Using a confidence level of 95% and a power of 90%, the minimum required sample size was calculated to be 39 cases.[ 1 ] Accordingly, 39 histopathologically confirmed colorectal adenomas were included in the study. Study Population Histopathologically diagnosed cases of colorectal adenomas received in the Department of Pathology during the study period constituted the study population. Inclusion and Exclusion Criteria Inclusion criteria Histopathologically confirmed cases of colorectal adenoma. Exclusion criteria Patients who had received chemotherapy and/or radiotherapy prior to tissue sampling Recurrent colorectal lesions Malignant colorectal neoplasms and non-adenomatous lesions Immunohistochemistry Method Formalin-fixed, paraffin-embedded tissue blocks of colorectal adenoma cases were retrieved. Sections of 4-µm thickness were cut and stained with hematoxylin and eosin to confirm histopathological diagnosis and grade of dysplasia. Immunohistochemical staining for Survivin was performed using a monoclonal antibody following standard immunohistochemical protocols. Survivin expression was assessed by evaluating the percentage of positively stained tumour cells in at least five high-power fields (400× magnification). Cases showing < 10% positive tumour cells were considered negative. Cases with 10–29%, 30–59%, and ≥ 60% positive tumour cells were graded as +, ++, and +++, respectively. Scoring was performed in a blinded manner. Statistical Analysis Data were entered into Microsoft Excel and analysed using SPSS version 24. Categorical variables were expressed as frequencies and percentages. The association between Survivin expression and grade of dysplasia in colorectal adenomas was analysed using the Chi-square test. A p value 55 years (85%), with a male predominance (60%). Site-wise distribution showed the rectum and transverse colon as the most commonly involved sites (22.5% each), followed by the descending colon (20%) and sigmoid colon (17.5%).(Table 1) Table 1: Demographic and Clinicopathological Profile of Colorectal Adenomas (n = 40) Parameter Category Number of Cases (%) Age (years) ≤55 6 (15.0) >55 34 (85.0) Gender Male 24 (60.0) Female 16 (40.0) Site Rectum 9 (22.5) Transverse colon 9 (22.5) Descending colon 8 (20.0) Sigmoid colon 7 (17.5) Ascending colon 5 (12.5) Cecum 2 (5.0) Based on histological grading, low-grade dysplasia (LGD) was observed in 24 cases (60%), while high-grade dysplasia (HGD) was present in 16 cases (40%). Regarding histological type, tubulovillous adenoma was the most common (50%), followed by tubular adenoma (42.5%) and villous adenoma (7.5%). (Table 2) Table 2: Distribution of Adenoma Type and Grade of Dysplasia (n = 40) Adenoma Type Number of Cases (%) Tubulovillous 20 (50.0) Tubular 17 (42.5) Villous 3 (7.5) Grade of Dysplasia Number of Cases (%) Low-grade dysplasia (LGD) 24 (60.0) High-grade dysplasia (HGD) 16 (40.0) Survivin expression was detected in a majority of adenoma cases and showed a significant association with the grade of dysplasia (Fig 1,2,3). In LGD, Survivin expression was predominantly low, with score 1+ in 54.2%, score 2+ in 41.7%, and score 3+ in 4.2% of cases. In contrast, HGD showed higher Survivin expression, with score 2+ in 62.5% and score 3+ in 37.5% of cases, and no cases with score 1+. This association between Survivin expression and grade of dysplasia was highly statistically significant (χ² = 15.595, df = 2, p < 0.001). (Table 3) Table 3: Survivin Expression in Colorectal Adenomas and Its Association with Dysplasia Grade (n = 40) Dysplasia Grade Survivin Score 1+ Survivin Score 2+ Survivin Score 3+ Total Low-grade (LGD) 13 (54.2%) 10 (41.7%) 1 (4.2%) 24 High-grade (HGD) 0 (0%) 10 (62.5%) 6 (37.5%) 16 Total 13 20 7 40 χ² = 15.595, df = 2, p < 0.001 DISCUSSION Colorectal adenomas represent the key precursor lesions in the adenoma–carcinoma sequence, and identifying molecular markers associated with dysplasia is critical for early detection and risk stratification.[ 10 , 11 , 12 ] In the present study, Survivin expression in adenomas was significantly associated with the grade of dysplasia, with high-grade dysplasia (HGD) cases showing markedly higher Survivin scores compared to low-grade dysplasia (LGD). This suggests that Survivin may contribute to early tumorigenic changes by promoting cell survival and resistance to apoptosis, thereby identifying adenomas with higher malignant potential. Our findings are consistent with several international studies. Lin et al. (2015) reported Survivin positivity in 30–35% of colorectal adenomas, with higher expression in lesions exhibiting advanced dysplasia, mirroring our observation of increased expression in HGD. (1) Similarly, a study by Hiroshi Kawasaki et al. (2001) demonstrated a stepwise increase in Survivin expression from low- to high-grade adenomas, supporting the role of Survivin as an early biomarker in the adenoma–carcinoma progression.[ 13 ] The concordance between our study and these reports underscores the reproducibility of Survivin as a marker of dysplasia across populations. In contrast, some studies have reported lower overall expression in adenomas or weaker correlation with dysplasia grade. These differences may be attributed to variations in antibody clones, immunohistochemical scoring criteria, sample size, and inclusion of mixed adenoma subtypes. For instance, studies including predominantly tubular adenomas may report lower Survivin positivity compared to studies with a higher proportion of tubulovillous or villous adenomas, which tend to exhibit greater dysplastic changes.[ 14 , 15 , 16 ] Mechanistically, Survivin’s overexpression in HGD adenomas aligns with its dual role in apoptosis inhibition and cell cycle regulation, facilitating clonal expansion of dysplastic epithelial cells.[ 17 , 18 , 19 ] This provides a biological rationale for its utility in risk stratification of adenomas, potentially identifying lesions more likely to progress toward carcinoma. Overall, the significant association between Survivin expression and dysplasia grade in our study reinforces its potential as a prognostic biomarker in colorectal adenomas, particularly in tertiary care settings in India where early identification of high-risk adenomas can guide surveillance and intervention strategies CONCLUSION Survivin expression in colorectal adenomas increases significantly with higher grades of dysplasia, highlighting its potential as a marker for identifying high-risk adenomas.[20,21] This study provides region-specific data from South India, reinforcing the role of Survivin in early malignant transformation and supporting its use in risk stratification and targeted surveillance of adenomatous lesions. Declarations Take-home message Survivin immunoexpression can help identify adenomas with higher malignant potential, guiding early intervention and follow-up strategies SOURCE OF SUPPORT Nil CONFLICT OF INTEREST None declared. AUTHORS’ CONTRIBUTIONS Concept and design: Shemeera Saidalavi Vellolipadikkal Data collection and analysis: Shemeera Saidalavi Vellolipadikkal Histopathological evaluation: All authors Manuscript drafting: Shemeera Saidalavi Vellolipadikkal Critical revision: All authors All authors read and approved the final manuscript. ACKNOWLEDGEMENT The authors acknowledge the Department of Pathology, Pushpagiri Medical College, for providing access to histopathological records and technical support for this study. DECLARATIONS Ethics approval and consent to participate The study was conducted after obtaining approval from the Institutional Ethics Committee of Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla (IEC Reg No. with DHR : EC/NEW/Inst/2020/1188). The study was performed in accordance with the ethical standards of the institutional research committee and the principles of the Declaration of Helsinki. As the study was based on archived histopathological specimens, patient confidentiality and anonymity were strictly maintained. Consent for publication Not applicable. The study does not contain any identifiable personal data or patient images requiring consent for publication. Availability of data and materials The datasets generated and analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors' contributions Shemeera Saidalavi Vellolipadikkal conceived and designed the study. Data collection, histopathological evaluation, and analysis were performed by the authors. Shemeera Saidalavi Vellolipadikkal drafted the manuscript. All authors critically revised the manuscript and approved the final version. Acknowledgements The authors acknowledge the Department of Pathology, Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, for providing access to histopathological records and laboratory facilities required for this study. References Lin LJ, Zheng CQ, Jin Y, Ma Y, Jiang WG, Ma T. Expression of survivin protein in human colorectal carcinogenesis with dysplasia and carcinoma. World J Gastroenterol . 2003;9(5):974–7. Kimura S, Aoki D, Yamada Y, Kawashima S, Ito K, Miyatake T. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis. Cancer . 2001;92(3):702–12. Hernandez JM, Farma JM, Coppola D, Hakam A, Fulp WJ, Chen DT, et al. Expression of the antiapoptotic protein survivin in colon cancer. Clin Colorectal Cancer . 2011;10(3):188–93. Al‑Maghrabi JA, Al‑Mansouri Z, Al‑Maghrabi J. Survivin expression is associated with lymph node metastasis and short survival in patients with colorectal adenocarcinoma and is present in adenomas. Int J Clin Exp Pathol . 2024;17(2):39–46. Tomicic MT, Kaina B. Survivin and molecular pathogenesis of colorectal cancer. Oncogene . 2003;22(27):4190–8. Schimmer AD. Survivin family proteins: clinical applications. Curr Opin Cell Biol . 2004;16(6):616–21. Altieri DC. Survivin, cancer networks and pathway‑directed drug discovery. Nat Rev Cancer . 2008;8(1):61–70. Duffy MJ, O’Donovan N, Brennan DJ, Gallagher WM. Survivin: role in diagnosis, prognosis and treatment of colorectal cancer. Crit Rev Oncol Hematol . 2007;62(2):105–20. Qiao L, Wong BC. Roles of survivin in colorectal cancer. Clin Colorectal Cancer . 2009;8(3):K1–K7. Mayor S, Too CK. Survivin expression in normal and neoplastic tissues. J Histochem Cytochem . 1999;47(9):1125–32. Minamoto T, Choueiri TK, Franklin W, et al. Expression of survivin and differential expression of apoptosis‑related genes in colorectal cancer. Clin Cancer Res . 2001;7(7):1970–6. Sarela AI, Macadam RC, Farmery SM, Markham AF, Guillou PJ. Early appearance of survivin expression in the normal mucosa–adenoma–carcinoma sequence. Gut . 2000;46(5):645–50. Kawasaki H, Altun M, Takahashi H, et al. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis. Cancer. 2001 Aktaş SH. Survivin as an immunohistochemical prognostic biomarker in colorectal cancer: a meta‑analysis. Turk J Oncol . 2022;37(4) Wang S, Xiao Y, An X, Luo L, Gong K, Yu D. A comprehensive review of survivin: function, clinical application, and prospects. Front Pharmacol . 2024;15:1336310. Sarela AI et al. Expression of survivin and its correlation with dysplasia grade in human colorectal neoplasia. J Clin Pathol . 2002;55(4) Martin V, Oba J, et al. Patterns of survivin expression in sporadic colorectal adenomas and dysplasia‑associated lesions. Int J Mol Sci . 2020;21(9):3260 Ponnelle T, Chapusot C, Martin L, Bouvier AM, Plenchette S, Faivre J, et al. Cellular localisation of survivin: impact on prognosis in colorectal cancer. J Cancer Res Clin Oncol . 2005;131(8):504–10. Hernandez JM, Farma JM. Survivin protein overexpression correlates with proliferation in colorectal tumors. Clin Cancer Res . 2011;17(7):188–93. Li F, Ackermann EJ, Bennett CF, et al. Down‑regulation of survivin causes apoptosis in colon cancer cells. Cancer Res . 1998;58(24):5071–4. Feng Q, Morin PJ, et al. Survivin as a therapeutic target: evidence from colorectal cancer models. Cancer Res . 2003;63(5):154–9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 01 Apr, 2026 Reviewers agreed at journal 31 Mar, 2026 Reviewers invited by journal 16 Mar, 2026 Editor assigned by journal 11 Mar, 2026 Submission checks completed at journal 11 Mar, 2026 First submitted to journal 07 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9060109","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606927974,"identity":"65b727bb-fe59-4be0-8ecd-a5ee6cfc04b5","order_by":0,"name":"Dr Shemeera Saidalavi Vellolipadikkal","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYDACCTiLsUHiA5BiYydFi+QMkBZm4rUwMEjzgEhCWuRnNx/d8KHinrx8++HG2za/tsnzMTMwfviYg1uLwZ1jaTdnnCk23HAmsdk6t++2YRszA7PkzG14tEjkmN3mbUtg3MCQ2Cad23ObEaiFjZkXjxb5Gfnfbv/9l2A/v/9hm7Rlz217gloYbuSw3WZsSEhsuAG0heHH7USCWgxupJnd7DmWkLzhxsNmy96G28ltzIzNeP0iPyP52Y0fNQm28/vTH9748ee27fz25oMfPuJzGApgbAOTDcSqB4E/pCgeBaNgFIyCkQIARq5WTHflJqUAAAAASUVORK5CYII=","orcid":"","institution":"Pushpagiri Institute of Medical Science and Research centre, Tiruvalla, Kerala","correspondingAuthor":true,"prefix":"Dr","firstName":"Shemeera","middleName":"Saidalavi","lastName":"Vellolipadikkal","suffix":""},{"id":606927975,"identity":"10146dd9-cbed-4257-8628-43534fe30bd8","order_by":1,"name":"Dr Lillykutty Pothen","email":"","orcid":"","institution":"Pushpagiri Institute of Medical Science and Research centre, Tiruvalla, Kerala","correspondingAuthor":false,"prefix":"Dr","firstName":"Lillykutty","middleName":"","lastName":"Pothen","suffix":""},{"id":606927976,"identity":"c61490cb-11a7-444c-a46f-dd731b21d5e2","order_by":2,"name":"Dr Jessy MM","email":"","orcid":"","institution":"Pushpagiri Institute of Medical Science and Research centre, Tiruvalla, Kerala","correspondingAuthor":false,"prefix":"Dr","firstName":"Jessy","middleName":"","lastName":"MM","suffix":""}],"badges":[],"createdAt":"2026-03-07 17:38:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9060109/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9060109/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104888529,"identity":"046ca49a-139d-473a-93c6-e9674c2b15b2","added_by":"auto","created_at":"2026-03-18 10:16:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":932479,"visible":true,"origin":"","legend":"\u003cp\u003eA:Tubular adenoma with focal LGD (H\u0026amp;E,4x), B: Survivin score 2+ in tubular adenoma with LGD (4x), C: Tubular adenoma with HGD(H\u0026amp;E,10x), \u0026nbsp;D: Survivin score 3+ in tubular adenoma with HGD(10x)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9060109/v1/80e20618fbf49c92e2ac01cd.png"},{"id":104888531,"identity":"285ea149-afe5-4ea4-b32c-7b8dcddceb67","added_by":"auto","created_at":"2026-03-18 10:16:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1089672,"visible":true,"origin":"","legend":"\u003cp\u003eA: Villous adenoma with LGD (H\u0026amp;E,10x), B: Survivin score 2+ in Villous adenoma with LGD (10x), C: Villous adenoma with LGD (H\u0026amp;E,10x), D: Survivin score 2+ in Villous adenoma with LGD (10x)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9060109/v1/183100330ce34962b9c84d24.png"},{"id":104888530,"identity":"4beda83e-0381-4e1e-885c-737504f285f6","added_by":"auto","created_at":"2026-03-18 10:16:52","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":971295,"visible":true,"origin":"","legend":"\u003cp\u003eA: Tubulovillous adenoma with LGD (H\u0026amp;E,4x), \u0026nbsp;B: Survivin score 2+ in Tubulovillous adenoma with LGD (4x), C: Tubulovillous adenoma with HGD (H\u0026amp;E,10x), B: Survivin score 3+ in Tubulovillous adenoma with HGD (10x)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9060109/v1/1996460f767ef3e5ce2512d6.png"},{"id":104888559,"identity":"b0467f1e-4272-4c6a-be0a-b5a652a7528e","added_by":"auto","created_at":"2026-03-18 10:17:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3855507,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9060109/v1/5c47139a-07f9-4dfb-8a4f-cc30c251d51b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eImmunohistochemical Expression of Survivin in Colorectal Adenomas and Its Correlation With Grade of Dysplasia - a Cross Sectional Study in a Tertiary Care Centre in South Kerala\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eColorectal cancer is one of the most common malignancies worldwide and commonly arises through the well-established adenoma\u0026ndash;carcinoma sequence.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The risk of malignant transformation increases with advancing grades of dysplasia in colorectal adenomas, highlighting the importance of identifying biomarkers that reflect early neoplastic progression.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSurvivin, the smallest member of the inhibitor of apoptosis protein family, plays a dual role in regulating apoptosis and cell proliferation. While Survivin expression is prominent during embryonic development, it is largely absent in normal adult tissues. Its re-expression has been demonstrated in a variety of human malignancies, including colorectal neoplasia, suggesting a role in tumor initiation and progression.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSeveral studies have shown increased Survivin expression in colorectal neoplasms, with higher expression reported in lesions showing advanced dysplasia. This supports the hypothesis that Survivin contributes to the adenoma\u0026ndash;carcinoma sequence by promoting cell survival and resistance to apoptosis during early tumorigenesis.\u003c/p\u003e \u003cp\u003eThe present study aims to evaluate the immunohistochemical expression of Survivin in colorectal adenomas and to assess its association with the grade of dysplasia, thereby exploring its potential role as a marker of neoplastic progression in colorectal adenomas.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis was a cross-sectional observational study conducted in the Department of Pathology, Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, over a period of 18 months following approval from the Institutional Ethics Committee.\u003c/p\u003e \u003cp\u003eSample Size\u003c/p\u003e \u003cp\u003eSample size was calculated based on a previous study by Lin et al., which reported Survivin positivity in 31.7% of colorectal adenomas. Using a confidence level of 95% and a power of 90%, the minimum required sample size was calculated to be 39 cases.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Accordingly, 39 histopathologically confirmed colorectal adenomas were included in the study.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population\u003c/h3\u003e\n\u003cp\u003eHistopathologically diagnosed cases of colorectal adenomas received in the Department of Pathology during the study period constituted the study population.\u003c/p\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria\u003c/h3\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eInclusion criteria\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eHistopathologically confirmed cases of colorectal adenoma.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eExclusion criteria\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003ePatients who had received chemotherapy and/or radiotherapy prior to tissue sampling\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eRecurrent colorectal lesions\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eMalignant colorectal neoplasms and non-adenomatous lesions\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eImmunohistochemistry Method\u003c/h2\u003e \u003cp\u003eFormalin-fixed, paraffin-embedded tissue blocks of colorectal adenoma cases were retrieved. Sections of 4-\u0026micro;m thickness were cut and stained with hematoxylin and eosin to confirm histopathological diagnosis and grade of dysplasia. Immunohistochemical staining for Survivin was performed using a monoclonal antibody following standard immunohistochemical protocols.\u003c/p\u003e \u003cp\u003eSurvivin expression was assessed by evaluating the percentage of positively stained tumour cells in at least five high-power fields (400\u0026times; magnification). Cases showing\u0026thinsp;\u0026lt;\u0026thinsp;10% positive tumour cells were considered negative. Cases with 10\u0026ndash;29%, 30\u0026ndash;59%, and \u0026ge;\u0026thinsp;60% positive tumour cells were graded as +, ++, and +++, respectively. Scoring was performed in a blinded manner.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were entered into Microsoft Excel and analysed using SPSS version 24. Categorical variables were expressed as frequencies and percentages. The association between Survivin expression and grade of dysplasia in colorectal adenomas was analysed using the Chi-square test. A p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe majority of adenoma cases occurred in patients aged \u0026gt;55 years (85%), with a male predominance (60%). Site-wise distribution showed the rectum and transverse colon as the most commonly involved sites (22.5% each), followed by the descending colon (20%) and sigmoid colon (17.5%).(Table 1)\u003c/p\u003e\n\u003cp\u003eTable 1: Demographic and Clinicopathological Profile of Colorectal Adenomas (n = 40)\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of Cases (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026le;55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e6 (15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u0026gt;55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e34 (85.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e24 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e16 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eRectum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e9 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eTransverse colon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e9 (22.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eDescending colon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e8 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eSigmoid colon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e7 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eAscending colon\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e5 (12.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 156px;\"\u003e\n \u003cp\u003eCecum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 204px;\"\u003e\n \u003cp\u003e2 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eBased on histological grading, low-grade dysplasia (LGD) was observed in 24 cases (60%), while high-grade dysplasia (HGD) was present in 16 cases (40%). Regarding histological type, tubulovillous adenoma was the most common (50%), followed by tubular adenoma (42.5%) and villous adenoma (7.5%). (Table 2)\u003c/p\u003e\n\u003cp\u003eTable 2: Distribution of Adenoma Type and Grade of Dysplasia (n = 40)\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdenoma Type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of Cases (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTubulovillous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20 (50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTubular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17 (42.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVillous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade of Dysplasia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of Cases (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLow-grade dysplasia (LGD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24 (60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHigh-grade dysplasia (HGD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16 (40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eSurvivin expression was detected in a majority of adenoma cases and showed a significant association with the grade of dysplasia (Fig 1,2,3). In LGD, Survivin expression was predominantly low, with score 1+ in 54.2%, score 2+ in 41.7%, and score 3+ in 4.2% of cases. In contrast, HGD showed higher Survivin expression, with score 2+ in 62.5% and score 3+ in 37.5% of cases, and no cases with score 1+. This association between Survivin expression and grade of dysplasia was highly statistically significant (\u0026chi;\u0026sup2; = 15.595, df = 2, p \u0026lt; 0.001). (Table 3)\u003c/p\u003e\n\u003cp\u003eTable 3: Survivin Expression in Colorectal Adenomas and Its Association with Dysplasia Grade (n = 40)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDysplasia Grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurvivin Score 1+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurvivin Score 2+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurvivin Score 3+\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLow-grade (LGD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13 (54.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (41.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1 (4.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHigh-grade (HGD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10 (62.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6 (37.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026chi;\u0026sup2; = 15.595, df = 2, p \u0026lt; 0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eColorectal adenomas represent the key precursor lesions in the adenoma\u0026ndash;carcinoma sequence, and identifying molecular markers associated with dysplasia is critical for early detection and risk stratification.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] In the present study, Survivin expression in adenomas was significantly associated with the grade of dysplasia, with high-grade dysplasia (HGD) cases showing markedly higher Survivin scores compared to low-grade dysplasia (LGD). This suggests that Survivin may contribute to early tumorigenic changes by promoting cell survival and resistance to apoptosis, thereby identifying adenomas with higher malignant potential.\u003c/p\u003e \u003cp\u003eOur findings are consistent with several international studies. Lin et al. (2015) reported Survivin positivity in 30\u0026ndash;35% of colorectal adenomas, with higher expression in lesions exhibiting advanced dysplasia, mirroring our observation of increased expression in HGD.\u003csup\u003e(1)\u003c/sup\u003e Similarly, a study by Hiroshi Kawasaki et al. (2001) demonstrated a stepwise increase in Survivin expression from low- to high-grade adenomas, supporting the role of Survivin as an early biomarker in the adenoma\u0026ndash;carcinoma progression.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] The concordance between our study and these reports underscores the reproducibility of Survivin as a marker of dysplasia across populations.\u003c/p\u003e \u003cp\u003eIn contrast, some studies have reported lower overall expression in adenomas or weaker correlation with dysplasia grade. These differences may be attributed to variations in antibody clones, immunohistochemical scoring criteria, sample size, and inclusion of mixed adenoma subtypes. For instance, studies including predominantly tubular adenomas may report lower Survivin positivity compared to studies with a higher proportion of tubulovillous or villous adenomas, which tend to exhibit greater dysplastic changes.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eMechanistically, Survivin\u0026rsquo;s overexpression in HGD adenomas aligns with its dual role in apoptosis inhibition and cell cycle regulation, facilitating clonal expansion of dysplastic epithelial cells.[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] This provides a biological rationale for its utility in risk stratification of adenomas, potentially identifying lesions more likely to progress toward carcinoma.\u003c/p\u003e \u003cp\u003eOverall, the significant association between Survivin expression and dysplasia grade in our study reinforces its potential as a prognostic biomarker in colorectal adenomas, particularly in tertiary care settings in India where early identification of high-risk adenomas can guide surveillance and intervention strategies\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eSurvivin expression in colorectal adenomas increases significantly with higher grades of dysplasia, highlighting its potential as a marker for identifying high-risk adenomas.[20,21] This study provides region-specific data from South India, reinforcing the role of Survivin in early malignant transformation and supporting its use in risk stratification and targeted surveillance of adenomatous lesions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eTake-home message\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;Survivin immunoexpression can help identify adenomas with higher malignant potential, guiding early intervention and follow-up strategies\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSOURCE OF SUPPORT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNil\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHORS’ CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eConcept and design:\u003c/strong\u003e Shemeera Saidalavi Vellolipadikkal\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eData collection and analysis:\u003c/strong\u003e Shemeera Saidalavi Vellolipadikkal\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eHistopathological evaluation:\u003c/strong\u003e All authors\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eManuscript drafting:\u003c/strong\u003e Shemeera Saidalavi Vellolipadikkal\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCritical revision:\u003c/strong\u003e All authors\u003cbr\u003e\u0026nbsp;All authors read and approved the final manuscript.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the Department of Pathology, Pushpagiri Medical College, for providing access to histopathological records and technical support for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eDECLARATIONS\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted after obtaining approval from the Institutional Ethics Committee of Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla (IEC Reg No. with DHR : EC/NEW/Inst/2020/1188). The study was performed in accordance with the ethical standards of the institutional research committee and the principles of the Declaration of Helsinki. As the study was based on archived histopathological specimens, patient confidentiality and anonymity were strictly maintained.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. The study does not contain any identifiable personal data or patient images requiring consent for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShemeera Saidalavi Vellolipadikkal conceived and designed the study. Data collection, histopathological evaluation, and analysis were performed by the authors. Shemeera Saidalavi Vellolipadikkal drafted the manuscript. All authors critically revised the manuscript and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge the Department of Pathology, Pushpagiri Institute of Medical Sciences and Research Centre, Tiruvalla, for providing access to histopathological records and laboratory facilities required for this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLin LJ, Zheng CQ, Jin Y, Ma Y, Jiang WG, Ma T. Expression of survivin protein in human colorectal carcinogenesis with dysplasia and carcinoma. \u003cem\u003eWorld J Gastroenterol\u003c/em\u003e. 2003;9(5):974\u0026ndash;7.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKimura S, Aoki D, Yamada Y, Kawashima S, Ito K, Miyatake T. Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis. \u003cem\u003eCancer\u003c/em\u003e. 2001;92(3):702\u0026ndash;12.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHernandez JM, Farma JM, Coppola D, Hakam A, Fulp WJ, Chen DT, et al. Expression of the antiapoptotic protein survivin in colon cancer. \u003cem\u003eClin Colorectal Cancer\u003c/em\u003e. 2011;10(3):188\u0026ndash;93.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAl‑Maghrabi JA, Al‑Mansouri Z, Al‑Maghrabi J. Survivin expression is associated with lymph node metastasis and short survival in patients with colorectal adenocarcinoma and is present in adenomas. \u003cem\u003eInt J Clin Exp Pathol\u003c/em\u003e. 2024;17(2):39\u0026ndash;46.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eTomicic MT, Kaina B. Survivin and molecular pathogenesis of colorectal cancer. \u003cem\u003eOncogene\u003c/em\u003e. 2003;22(27):4190\u0026ndash;8.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSchimmer AD. Survivin family proteins: clinical applications. \u003cem\u003eCurr Opin Cell Biol\u003c/em\u003e. 2004;16(6):616\u0026ndash;21.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAltieri DC. Survivin, cancer networks and pathway‑directed drug discovery. \u003cem\u003eNat Rev Cancer\u003c/em\u003e. 2008;8(1):61\u0026ndash;70.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDuffy MJ, O\u0026rsquo;Donovan N, Brennan DJ, Gallagher WM. Survivin: role in diagnosis, prognosis and treatment of colorectal cancer. \u003cem\u003eCrit Rev Oncol Hematol\u003c/em\u003e. 2007;62(2):105\u0026ndash;20.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eQiao L, Wong BC. Roles of survivin in colorectal cancer. \u003cem\u003eClin Colorectal Cancer\u003c/em\u003e. 2009;8(3):K1\u0026ndash;K7.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMayor S, Too CK. Survivin expression in normal and neoplastic tissues. \u003cem\u003eJ Histochem Cytochem\u003c/em\u003e. 1999;47(9):1125\u0026ndash;32.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMinamoto T, Choueiri TK, Franklin W, et al. Expression of survivin and differential expression of apoptosis‑related genes in colorectal cancer. \u003cem\u003eClin Cancer Res\u003c/em\u003e. 2001;7(7):1970\u0026ndash;6.\u003c/li\u003e\n \u003cli\u003eSarela AI, Macadam RC, Farmery SM, Markham AF, Guillou PJ. Early appearance of survivin expression in the normal mucosa\u0026ndash;adenoma\u0026ndash;carcinoma sequence. \u003cem\u003eGut\u003c/em\u003e. 2000;46(5):645\u0026ndash;50.\u003c/li\u003e\n \u003cli\u003eKawasaki H, Altun M, Takahashi H, et al. \u003cem\u003eExpression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis.\u003c/em\u003e Cancer. 2001\u003c/li\u003e\n \u003cli\u003eAktaş SH. Survivin as an immunohistochemical prognostic biomarker in colorectal cancer: a meta‑analysis. \u003cem\u003eTurk J Oncol\u003c/em\u003e. 2022;37(4)\u003c/li\u003e\n \u003cli\u003eWang S, Xiao Y, An X, Luo L, Gong K, Yu D. A comprehensive review of survivin: function, clinical application, and prospects. \u003cem\u003eFront Pharmacol\u003c/em\u003e. 2024;15:1336310.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSarela AI et al. Expression of survivin and its correlation with dysplasia grade in human colorectal neoplasia. \u003cem\u003eJ Clin Pathol\u003c/em\u003e. 2002;55(4)\u003c/li\u003e\n \u003cli\u003eMartin V, Oba J, et al. Patterns of survivin expression in sporadic colorectal adenomas and dysplasia‑associated lesions. \u003cem\u003eInt J Mol Sci\u003c/em\u003e. 2020;21(9):3260\u003c/li\u003e\n \u003cli\u003ePonnelle T, Chapusot C, Martin L, Bouvier AM, Plenchette S, Faivre J, et al. Cellular localisation of survivin: impact on prognosis in colorectal cancer. \u003cem\u003eJ Cancer Res Clin Oncol\u003c/em\u003e. 2005;131(8):504\u0026ndash;10.\u003c/li\u003e\n \u003cli\u003eHernandez JM, Farma JM. Survivin protein overexpression correlates with proliferation in colorectal tumors. \u003cem\u003eClin Cancer Res\u003c/em\u003e. 2011;17(7):188\u0026ndash;93.\u003c/li\u003e\n \u003cli\u003eLi F, Ackermann EJ, Bennett CF, et al. Down‑regulation of survivin causes apoptosis in colon cancer cells. \u003cem\u003eCancer Res\u003c/em\u003e. 1998;58(24):5071\u0026ndash;4.\u003c/li\u003e\n \u003cli\u003eFeng Q, Morin PJ, et al. Survivin as a therapeutic target: evidence from colorectal cancer models. \u003cem\u003eCancer Res\u003c/em\u003e. 2003;63(5):154\u0026ndash;9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":false,"email":"[email protected]","identity":"surgical-and-experimental-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"saep","sideBox":"Learn more about [Surgical and Experimental Pathology](http://surgexppathol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/SAEP/default.aspx","title":"Surgical and Experimental Pathology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Colorectal adenoma, dysplasia, immunohistochemistry, Survivin","lastPublishedDoi":"10.21203/rs.3.rs-9060109/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9060109/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eColorectal cancer commonly develops through the adenoma\u0026ndash;carcinoma sequence. Survivin, a member of the inhibitor of apoptosis protein family, regulates apoptosis and cell proliferation and is minimally expressed in normal adult tissues. Its re-expression in colorectal neoplasia suggests a role in early tumorigenesis and progression.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo evaluate the immunohistochemical expression of Survivin in colorectal adenomas and to assess its association with the grade of dysplasia.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eThis cross-sectional study included 40 cases of colorectal adenomas selected by consecutive sampling after ethical clearance. Clinicopathological details were recorded. Histomorphological assessment was performed, followed by immunohistochemical evaluation of Survivin expression. The expression pattern was analysed and correlated with the grade of dysplasia.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSurvivin expression was detected in a significant proportion of colorectal adenomas. A statistically significant increase in Survivin expression was observed with increasing grades of dysplasia, with higher expression noted in high-grade dysplasia compared to low-grade dysplasia.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSurvivin expression shows a significant association with increasing grades of dysplasia in colorectal adenomas, supporting its role in early colorectal tumorigenesis. Immunohistochemical assessment of Survivin may help identify adenomas with higher malignant potential.\u003c/p\u003e","manuscriptTitle":"Immunohistochemical Expression of Survivin in Colorectal Adenomas and Its Correlation With Grade of Dysplasia - a Cross Sectional Study in a Tertiary Care Centre in South Kerala","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-18 10:16:47","doi":"10.21203/rs.3.rs-9060109/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"289631311169199380468414463930171863738","date":"2026-04-02T02:54:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"169290265718687457976338883776719274061","date":"2026-04-01T00:50:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-16T12:36:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-11T07:19:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-11T07:18:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"Surgical and Experimental Pathology","date":"2026-03-07T17:21:46+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":false,"email":"[email protected]","identity":"surgical-and-experimental-pathology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"saep","sideBox":"Learn more about [Surgical and Experimental Pathology](http://surgexppathol.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/SAEP/default.aspx","title":"Surgical and Experimental Pathology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0e3ee5c9-453b-4c52-9485-80309788b95c","owner":[],"postedDate":"March 18th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-18T10:16:47+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-18 10:16:47","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9060109","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9060109","identity":"rs-9060109","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}