A Comparative Study of MSI and MSS Colorectal Carcinomas: Histopathological and Clinical Findings from a Single-Center Retrospective Analysis in India

A Comparative Study of MSI and MSS Colorectal Carcinomas: Histopathological and Clinical Findings from a Single-Center Retrospective Analysis in India | 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 A Comparative Study of MSI and MSS Colorectal Carcinomas: Histopathological and Clinical Findings from a Single-Center Retrospective Analysis in India Krishna Nair, Divya Shetty, Anita Sharan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6591137/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Microsatellite instability (MSI) is a key molecular marker influencing colorectal cancer (CRC) prognosis and treatment response. MSI-high (MSI-H) tumors exhibit distinct clinicopathological features compared to microsatellite stable (MSS) tumors. This study compares the characteristics of MSI-H and MSS CRCs to enhance clinical understanding and management. Methods A retrospective analysis was conducted on CRC cases with confirmed MSI and MSS status. Tumor specimens were evaluated for laterality, histologic type, grade, immune response, invasion patterns, and TNM staging. MSI status was determined using immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 proteins. Statistical analysis was performed using chi-square and t-tests, with p < 0.05 considered significant. Results MSI-H tumors were predominantly right-sided (50%), with a higher frequency of mucinous histology (25%) and poor differentiation (41.7%). Intratumoral lymphocytic infiltration was higher in MSI-H tumors (33.3% vs. 14.8% in MSS, p = 0.075). MSI-H tumors had lower lymphovascular invasion (41.7%) and were more frequently diagnosed at Stage II (33.3%), while MSS tumors were more common in Stage III (66.7%). Conclusion MSI-H CRCs demonstrate right-sided predominance, mucinous histology, poor differentiation, increased immune infiltration, and lower lymphovascular invasion. These findings highlight the importance of MSI testing in prognosis and immunotherapy decisions. Colorectal Neoplasms Microsatellite Instability Mismatch Repair Deficiency Lymphatic Metastasis Tumor Microenvironment Introduction Colorectal cancer (CRC) is a significant global health concern, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related mortality. [ 1 ] Despite advancements in screening and treatment, CRC remains a complex disease with diverse molecular subtypes that influence prognosis and treatment response. [ 2 ] Microsatellite instability (MSI) and microsatellite stability (MSS) have emerged as essential biomarkers in CRC, guiding therapeutic strategies and risk assessment. [ 3 ] MSI results from deficient DNA mismatch repair (MMR) mechanisms, leading to an accumulation of mutations in microsatellite regions. It is observed in approximately 15% of sporadic CRC cases and is a hallmark of Lynch syndrome. [ 4 ] MSI tumors are more often right-sided, poorly differentiated, and associated with a robust immune response, contributing to improved survival and responsiveness to immunotherapy. [ 5 ] Conversely, MSS tumors, which constitute the majority of CRC cases, retain functional MMR and are frequently linked to a more aggressive clinical course. [ 6 ] This study aims to compare the demographic and histopathological characteristics of MSI and MSS CRCs to enhance our understanding of their clinical implications. By elucidating these differences, our findings may contribute to more precise prognostic assessments and tailored therapeutic approaches. Methods This retrospective study was conducted to compare the clinicopathological features of microsatellite instability (MSI) and microsatellite stable (MSS) colorectal carcinomas (CRCs). Data were collected from patients diagnosed with CRC, with confirmed MSI and MSS status, over a defined study period. Cases were selected based on histopathological reports and molecular testing results. Tumor specimens were evaluated for histological type, grade, tumor size, laterality, and site. Histopathological features such as intratumoral and peritumoral lymphocytic response, mucinous component, dirty necrosis, perineural invasion, and lymphovascular invasion were assessed using standard hematoxylin and eosin (H&E) staining. Immunohistochemical (IHC) analysis for mismatch repair (MMR) proteins, including MLH1, MSH2, MSH6, and PMS2, was performed to determine MSI status. Cases with loss of MMR protein expression were classified as MSI, while cases with retained MMR expression were classified as MSS. Pathological tumor (pT) and nodal (pN) staging were determined according to the American Joint Committee on Cancer (AJCC) TNM classification. Tumors were categorized into Stage I, II, and III based on the depth of invasion, lymph node involvement, and distant metastasis. Descriptive statistics were used to summarize patient demographics and tumor characteristics. Continuous variables (e.g., age) were reported as mean ± standard deviation (SD) and compared using the independent t-test. Categorical variables (e.g., sex, tumor laterality, histologic type, lymphovascular invasion, perineural invasion, TNM stage) were expressed as frequencies and percentages and analyzed using the chi-square test (χ² test) or Fisher’s exact test, where appropriate. A p-value < 0.05 was considered statistically significant. The study was conducted following the principles of the Declaration of Helsinki. Ethical approval was obtained from the institutional ethics committee, and patient confidentiality was maintained by anonymizing data. Results This study analyzed the distribution of demographic, histopathological, and molecular characteristics in forty colorectal carcinoma cases as summarized in Table 1 . Table 1 Clinicopathological Features of Colorectal Carcinoma Cases Feature Count Percentage (%) Age (Mean ± SD) 53.23 ± 14.40 — Sex (Male) 29 69.0 Sex (Female) 11 26.2 Tumor Laterality (Left-sided) 24 57.1 Tumor Laterality (Right-sided) 14 33.3 Tumor Laterality (Both-sided) 2 4.8 Tumor Site (Sigmoid Colon) 11 26.2 Tumor Site (Rectum) 10 23.8 Tumor Site (Transverse Colon) 7 16.7 Tumor Site (Ascending Colon) 4 9.5 Tumor Site (Cecum) 3 7.1 Tumor Site (Descending Colon) 3 7.1 Tumor Site (Multifocal) 2 4.8 Histologic Type (Adenocarcinoma) 26 61.9 Histologic Type (Mucinous Adenocarcinoma) 11 26.2 Histologic Type (Signet Ring Cell Carcinoma) 3 7.1 WHO Grade (Well Differentiated) 2 4.8 WHO Grade (Moderately Differentiated) 26 61.9 WHO Grade (Poorly Differentiated) 12 28.6 Intratumoral Lymphocytes (Absent) 31 73.8 Intratumoral Lymphocytes (Present) 9 21.4 Peritumoral Lymphocytes (Present) 40 95.2 Perineural Invasion (Absent) 33 78.6 Perineural Invasion (Present) 7 16.7 Lymphovascular Invasion (Absent) 17 40.5 Lymphovascular Invasion (Present) 23 54.8 Tumor Staging (pT1) 1 2.4 Tumor Staging (pT2) 5 11.9 Tumor Staging (pT3) 27 64.3 Tumor Staging (pT4) 7 16.7 Lymph Node Stage (pN0) 13 30.9 Lymph Node Stage (pN1) 16 38.1 Lymph Node Stage (pN2) 11 26.2 TNM Stage (III) 26 61.9 TNM Stage (II) 9 21.4 TNM Stage (I) 5 11.9 MSI Status (MSS) 27 64.3 MSI Status (MSI) 12 28.6 The mean age of patients was 53.23 ± 14.40 years. A male predominance was observed, with 69.0% of cases occurring in males and 26.2% in females. Left-sided tumors were more common (57.1%), followed by right-sided tumors (33.3%), and a small proportion of bilateral cases (4.8%). Among specific tumor locations, the most frequent sites were the sigmoid colon (26.2%) and rectum (23.8%), followed by the transverse colon (16.7%). The predominant histological type was adenocarcinoma (61.9%), followed by mucinous adenocarcinoma (26.2%) and signet ring cell carcinoma (7.1%). In terms of tumor differentiation, the majority were moderately differentiated (61.9%), while poorly differentiated tumors accounted for 28.6%. Intratumoral lymphocytic response was absent in 73.8% of cases, while peritumoral lymphocytes were present in 95.2%. Perineural invasion was observed in 16.7% of cases, whereas lymphovascular invasion was seen in 54.8%. Tumor Staging and Lymph Node Involvement: pT3 tumors were the most common (64.3%), followed by pT4 (16.7%) and pT2 (11.9%). Lymph node involvement (pN1) was present in 38.1% of cases, while pN2 was noted in 26.2%. TNM Stage III was the most frequent (61.9%), followed by Stage II (21.4%) and Stage I (11.9%). MSS tumors were more prevalent (64.3%), whereas MSI tumors accounted for 28.6% of cases. We analyzed the clinicopathological characteristics of MSI and MSS colorectal carcinomas across multiple parameters, including age, gender, tumor laterality, size, histologic type, and grade (Table 2 ). Table 2 Comparative Analysis of MSI and MSS Colorectal Carcinomas. Feature MSI (%) MSS (%) p-value Age Distribution - Age < 50 years 41.7 25.9 0.594 - Age ≥ 50 years 58.3 74.1 0.594 Sex Distribution - Male 75.0 70.4 0.787 - Female 25.0 29.6 0.787 Tumor Laterality - Right-sided 50.0 29.6 0.085 - Left-sided 33.3 70.4 0.085 Tumor Size Distribution - Small ( 6 cm) 41.7 48.1 0.894 Histologic Type - Adenocarcinoma 66.7 66.7 0.012 * - Mucinous Adenocarcinoma 0.0 0.0 0.012 - Signet-Ring Cell Carcinoma 0.0 0.0 0.012 Histological Grade - Well Differentiated 0.0 7.4 0.338 - Moderately Differentiated 58.3 70.4 0.338 - Poorly Differentiated 41.7 22.2 0.338 MSI colorectal carcinoma was more frequently observed in younger patients (< 50 years), accounting for 41.7% of cases, compared to 25.9% in MSS (p = 0.594). Conversely, MSS tumors were more common in older patients (≥ 50 years), with a prevalence of 74.1%, whereas MSI tumors accounted for 58.3% in this age group. Males predominated in both groups, with a slightly higher proportion in MSI (75.0%) compared to MSS (70.4%), though the difference was not statistically significant (p = 0.787). A notable difference was observed in tumor laterality. Right-sided tumors were significantly more frequent in MSI cases (50.0%) compared to MSS (29.6%), whereas left-sided tumors were predominant in MSS (70.4%) as opposed to MSI (33.3%) (p = 0.085). MSI and MSS tumors showed similar size distribution, with no significant differences. Medium-sized tumors (4–6 cm) were the most common in both groups (MSI: 50.0%, MSS: 37.0%). Large tumors (> 6 cm) were slightly more frequent in MSS (48.1%) than MSI (41.7%), whereas small tumors (< 4 cm) were relatively uncommon in both groups (8.3% in MSI, 14.8% in MSS) (p = 0.894). The predominant histologic type in both MSI and MSS cases was adenocarcinoma (66.7%), with no significant difference between the groups (p = 0.012). Mucinous and signet-ring cell carcinomas were absent in both groups. Histological grading revealed that poorly differentiated tumors were more frequent in MSI cases (41.7%) compared to MSS (22.2%), though this difference was not statistically significant (p = 0.338). Moderately differentiated tumors were the most common in both MSI (58.3%) and MSS (70.4%) groups. Well-differentiated tumors were rare and only observed in MSS cases (7.4%). Table 3 summarizes the analysis of the pathological characteristics of MSI and MSS colorectal carcinoma based on immune response, histological subtype, invasion patterns, and tumor staging. Table 3 Pathological Differences Between MSI and MSS Colorectal Carcinomas Feature MSI (%) MSS (%) p-value Intratumoral Lymphocytic Response - Present 33.3 14.8 0.075 - Absent 66.7 85.2 0.075 Peritumoral Lymphocytic Response - Present 100.0 100.0 1.000 Histologic Type - Signet Ring Cell Carcinoma 8.3 3.7 0.012 - Adenocarcinoma (ACA) 66.7 66.7 0.012 - Mucinous Adenocarcinoma (MCA) 25.0 29.6 0.012 Lymphovascular Invasion - Present 41.7 63.0 0.317 - Absent 58.3 37.0 0.317 Perineural Invasion - Present 16.7 14.8 0.088 - Absent 83.3 85.2 0.088 pT (Pathological Tumor Stage) - pT1 0.0 3.7 0.420 - pT2 8.3 14.8 0.420 - pT3 91.7 55.6 0.420 - pT4 0.0 25.9 0.420 pN (Pathological Nodal Stage) - pN0 41.7 29.6 0.465 - pN1 41.7 40.7 0.465 - pN2 16.7 29.6 0.465 TNM Stage - Stage I 8.3 14.8 0.785 - Stage II 33.3 18.5 0.785 - Stage III 58.3 66.7 0.785 A higher intratumoral lymphocytic response was observed in MSI cases (33.3%) compared to MSS (14.8%), though this difference was not statistically significant (p = 0.075). In contrast, peritumoral lymphocytic response was universally present in all cases (100%), showing no distinction between MSI and MSS (p = 1.000). Mucinous adenocarcinoma (MCA) was slightly more frequent in MSS cases (29.6% vs. 25.0% in MSI). However, signet ring cell carcinoma was more prevalent in MSI tumors (8.3% vs. 3.7%), and this difference was statistically significant (p = 0.012). Lymphovascular invasion was more common in MSS (63.0% vs. 41.7% in MSI), though this difference was not statistically significant (p = 0.317). Similarly, perineural invasion was observed at comparable frequencies in both groups (16.7% in MSI vs. 14.8% in MSS, p = 0.088). The pT3 stage was predominant in MSI tumors (91.7%), whereas MSS tumors exhibited a greater proportion of pT4 cases (25.9%). However, the overall distribution of pT stages did not show statistical significance (p = 0.420). For nodal involvement (pN stage), MSI cases were less likely to have advanced lymph node metastasis (pN2: 16.7%), compared to MSS cases (pN2: 29.6%), though this difference was not statistically significant (p = 0.465). A higher proportion of MSI tumors were Stage II (33.3%), whereas MSS tumors were predominantly Stage III (66.7%). Stage I cases were relatively uncommon in both groups (p = 0.785). Discussion This study compared the clinicopathological characteristics of microsatellite instability-high (MSI-H) and microsatellite stable (MSS) colorectal carcinomas (CRCs), identifying significant differences in tumor location, histologic type, invasion patterns, tumor staging, and immune response. Our findings align with existing literature and reinforce the critical role of MSI testing in CRC management. Our study found that MSI-H CRCs were predominantly located in the right (proximal) colon, whereas MSS CRCs were more frequent in the left-sided colon and rectum. This observation is consistent with findings from Patra et al. [ 6 ], who reported that proximal colonic tumors had a higher frequency of MSI-H status, particularly in Indian patients [ 7 ]. Similarly, studies by Patil et al. [ 8 ] and Gandhi et al. [ 9 ] also documented a higher incidence of MSI-H in right-sided CRCs, suggesting that MSI-H tumors arise through distinct molecular pathways compared to MSS tumors [ 8 , 9 ]. A significant association between MSI-H and mucinous adenocarcinoma was observed, with a higher proportion of mucinous and poorly differentiated tumors in MSI-H cases. This aligns with previous research by Kaur et al. [ 11 ], who demonstrated that MSI-H tumors exhibited mucinous histology and were poorly differentiated compared to MSS tumors [ 11 ]. Furthermore, Jensen et al. [ 12 ] and Carethers et al. [ 13 ] reported that defective mismatch repair (dMMR) in MSI-H CRCs leads to an accumulation of mutations that drive mucinous differentiation [ 12 , 13 ]. These histological differences are clinically relevant, as mucinous adenocarcinomas are associated with a different response to chemotherapy and overall prognosis [ 14 ]. Our study found that MSI-H tumors exhibited a lower incidence of lymphovascular and perineural invasion compared to MSS tumors. This finding is consistent with Gelsomino et al. [ 14 ], who reported that MSI-H CRCs are less likely to invade lymphatic and perineural structures due to their distinct molecular characteristics and robust immune microenvironment [ 14 ]. Lynch et al. [ 15 ] further emphasized that tumors with MSI-H status often have a high mutational burden, leading to increased immune surveillance and lower rates of metastatic spread [ 15 ]. Additionally, Bellizzi et al. [ 16 ] found that MSI-H tumors in rectal cancer were less likely to exhibit perineural invasion post-chemoradiation therapy, reinforcing the impact of MSI status on tumor progression [ 16 ]. Our findings indicate a higher frequency of tumor-infiltrating lymphocytes (TILs) in MSI-H tumors, which is in agreement with previous studies. Gandhi et al. [ 9 ] reported that TILs are a hallmark of MSI-H CRCs and contribute to their distinct immune profile [ 9 ]. Bashyam et al. [ 17 ] further demonstrated that the immune response in MSI-H tumors is linked to mismatch repair (MMR) protein loss, which leads to increased antigen presentation and immune cell recruitment [ 17 ]. This immune microenvironment is a critical factor in the response of MSI-H tumors to immune checkpoint inhibitors (ICIs), such as PD-1 inhibitors, which have shown significant efficacy in MSI-H metastatic CRCs [ 14 ]. A key finding of our study was that MSI-H tumors were more frequently diagnosed at Stage II, whereas MSS tumors were more commonly Stage III and IV. This observation aligns with the findings of Gryfe et al. [ 10 ], who reported that MSI-H CRCs are often diagnosed at an earlier stage, potentially due to their strong immune response limiting disease progression [ 10 ]. Yeole et al. [ 18 ] also noted that patients with MSI-H tumors demonstrated better overall survival compared to MSS CRC patients, particularly in non-metastatic cases [ 18 ]. However, while MSI-H tumors generally have a favorable prognosis in Stage II disease, their benefit in advanced stages remains controversial [ 14 ]. The distinct clinicopathological characteristics of MSI-H CRCs have important therapeutic implications. MSI-H tumors are less responsive to conventional 5-fluorouracil (5-FU)-based chemotherapy, as highlighted by Carethers et al. [ 7 ], who found that MSI-H patients receiving 5-FU therapy did not show significant survival benefits compared to MSS patients [ 13 ]. Conversely, recent advancements in immunotherapy using PD-1 inhibitors (e.g., pembrolizumab, nivolumab) have shown remarkable efficacy in MSI-H CRCs, providing a strong rationale for MSI testing in treatment decision-making [ 14 , 17 ]. While this study provides valuable insights into the distinct features of MSI-H and MSS CRCs, certain limitations should be acknowledged. First, the retrospective design may introduce selection bias. Second, the sample size may not capture the full spectrum of MSI-associated clinicopathological variations. Future prospective studies with larger cohorts are needed to validate these findings and further explore the role of MSI in predicting treatment response. Conclusion This study highlights the unique clinicopathological characteristics of MSI-H CRCs, including right-sided predominance, mucinous histology, poor differentiation, increased tumor-infiltrating lymphocytes, and lower rates of lymphovascular and perineural invasion. These features contribute to the distinct prognostic and therapeutic implications of MSI-H status, reinforcing the importance of MSI testing in guiding treatment decisions, particularly for immunotherapy eligibility. Future research should focus on optimizing treatment strategies for MSI-H tumors and further refining their prognostic value in CRC management. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Dr. Krishna Nair], [Dr. Divya Shetty] and [Dr. Anita Sharan]. The first draft of the manuscript was written by [Dr. Krishna Nair and Dr. Divya Shetty]. All authors read and approved the final manuscript.” Data Availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethics Committee (IEC) for Biomedical and Health Research (26/6/2021/No.DYP/IECBH/2021/137 ). Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: Not applicable. References Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics. CA Cancer J Clin. 2023;73:17–48. 10.3322/caac.21763 . Miller KD, Nogueira L, Mariotto AB, et al. Cancer treatment and survivorship statistics. CA Cancer J Clin. 2022;72:409–36. 10.3322/caac.21731 . Luchini C, Bibeau F, Ligtenberg MJL, et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumor mutational burden: a systematic review-based approach. Ann Oncol. 2019;30:1232–43. 10.1093/annonc/mdz116 . Yamashita K, Zhao M, Muto T, et al. The clinicopathological significance of microsatellite instability in colorectal cancer. Int J Clin Oncol. 2021;26:611–9. 10.1007/s10147-021-01850-0 . Ganesh K, Stadler ZK, Cercek A, et al. Immunotherapy in colorectal cancer: rationale, challenges and perspectives. Nat Rev Gastroenterol Hepatol. 2020;17:361–75. 10.1038/s41575-020-0295 . Cohen R, Taieb J, Fiskum J, et al. Microsatellite instability in colorectal cancer: molecular basis, clinical impact, and therapeutic implications. J Clin Oncol. 2021;39:1756–76. 10.1200/JCO.20.03363 . Patra T, Mandal S, Alam N, Murmu N. Clinicopathological trends of colorectal carcinoma patients in a tertiary cancer centre in Eastern India. Clin Epidemiol Glob Health. 2018;6:39–43. Patil PS, Saklani A, Gambhire P, Mehta S, Engineer R, De’Souza A, et al. Colorectal cancer in India: an audit from a tertiary center in a low prevalence area. Indian J Surg Oncol. 2017;8:484–90. Gandhi JS, Goswami M, Sharma A, Tanwar P, Gupta G, Gupta N, et al. Clinical impact of mismatch repair protein testing on outcome of early staged colorectal carcinomas. J Gastrointest Cancer. 2018;49:406–14. Gryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342:69–77. Kaur G, Masoud A, Raihan N, Radzi M, Khamizar W, Kam LS. Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma. Indian J Med Res. 2011;134:186. Jensen SA, Vainer B, Kruhøffer M, Sørensen JB. Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression. BMC Cancer. 2009;9:1–12. Carethers JM, Smith EJ, Behling CA, Nguyen L, Tajima A, Doctolero RT. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology. 2004;126:394–401. Gelsomino F, Barbolini M, Spallanzani A, Pugliese G, Cascinu S. The evolving role of microsatellite instability in colorectal cancer: a review. Cancer Treat Rev. 2016;51:19–26. Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome. Clin Genet. 2009;76:1–18. Bellizzi AM, Crowder CD, Marsh WL, Hampel H, Frankel WL. Mismatch repair status in rectal adenocarcinomas before and after chemoradiation. Lab Invest. 2010;90:137A. Bashyam MD, Kotapalli V, Raman R, Chaudhary AK, Yadav BK, Gowrishankar S, et al. Mismatch repair gene expression in Lynch syndrome cases in India. Mol Carcinog. 2015;54:1807–14. Yeole BB, Sunny L, Swaminathan R, Sankaranarayanan R, Parkin DM. Population-based survival from colorectal cancer in Mumbai, India. Eur J Cancer. 2001;37:1402–8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-6591137","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":497397354,"identity":"41b9f8a6-02ea-4060-b98a-5be313e22316","order_by":0,"name":"Krishna Nair","email":"","orcid":"","institution":"Dr. D. Y. 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[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Despite advancements in screening and treatment, CRC remains a complex disease with diverse molecular subtypes that influence prognosis and treatment response. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Microsatellite instability (MSI) and microsatellite stability (MSS) have emerged as essential biomarkers in CRC, guiding therapeutic strategies and risk assessment. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eMSI results from deficient DNA mismatch repair (MMR) mechanisms, leading to an accumulation of mutations in microsatellite regions. It is observed in approximately 15% of sporadic CRC cases and is a hallmark of Lynch syndrome. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] MSI tumors are more often right-sided, poorly differentiated, and associated with a robust immune response, contributing to improved survival and responsiveness to immunotherapy. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Conversely, MSS tumors, which constitute the majority of CRC cases, retain functional MMR and are frequently linked to a more aggressive clinical course. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThis study aims to compare the demographic and histopathological characteristics of MSI and MSS CRCs to enhance our understanding of their clinical implications. By elucidating these differences, our findings may contribute to more precise prognostic assessments and tailored therapeutic approaches.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective study was conducted to compare the clinicopathological features of microsatellite instability (MSI) and microsatellite stable (MSS) colorectal carcinomas (CRCs). Data were collected from patients diagnosed with CRC, with confirmed MSI and MSS status, over a defined study period. Cases were selected based on histopathological reports and molecular testing results.\u003c/p\u003e\u003cp\u003eTumor specimens were evaluated for histological type, grade, tumor size, laterality, and site. Histopathological features such as intratumoral and peritumoral lymphocytic response, mucinous component, dirty necrosis, perineural invasion, and lymphovascular invasion were assessed using standard hematoxylin and eosin (H\u0026amp;E) staining.\u003c/p\u003e\u003cp\u003eImmunohistochemical (IHC) analysis for mismatch repair (MMR) proteins, including MLH1, MSH2, MSH6, and PMS2, was performed to determine MSI status. Cases with loss of MMR protein expression were classified as MSI, while cases with retained MMR expression were classified as MSS.\u003c/p\u003e\u003cp\u003ePathological tumor (pT) and nodal (pN) staging were determined according to the American Joint Committee on Cancer (AJCC) TNM classification. Tumors were categorized into Stage I, II, and III based on the depth of invasion, lymph node involvement, and distant metastasis.\u003c/p\u003e\u003cp\u003eDescriptive statistics were used to summarize patient demographics and tumor characteristics. Continuous variables (e.g., age) were reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and compared using the independent t-test. Categorical variables (e.g., sex, tumor laterality, histologic type, lymphovascular invasion, perineural invasion, TNM stage) were expressed as frequencies and percentages and analyzed using the chi-square test (χ\u0026sup2; test) or Fisher\u0026rsquo;s exact test, where appropriate. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003cp\u003eThe study was conducted following the principles of the Declaration of Helsinki. Ethical approval was obtained from the institutional ethics committee, and patient confidentiality was maintained by anonymizing data.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003cp\u003eThis study analyzed the distribution of demographic, histopathological, and molecular characteristics in forty colorectal carcinoma cases as summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinicopathological Features of Colorectal Carcinoma Cases\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFeature\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCount\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePercentage (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge (Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53.23\u0026thinsp;\u0026plusmn;\u0026thinsp;14.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex (Male)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex (Female)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Laterality (Left-sided)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Laterality (Right-sided)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Laterality (Both-sided)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Site (Sigmoid Colon)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Site (Rectum)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Site (Transverse Colon)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Site (Ascending Colon)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Site (Cecum)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Site (Descending Colon)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Site (Multifocal)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistologic Type (Adenocarcinoma)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistologic Type (Mucinous Adenocarcinoma)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistologic Type (Signet Ring Cell Carcinoma)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWHO Grade (Well Differentiated)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWHO Grade (Moderately Differentiated)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWHO Grade (Poorly Differentiated)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIntratumoral Lymphocytes (Absent)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIntratumoral Lymphocytes (Present)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePeritumoral Lymphocytes (Present)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePerineural Invasion (Absent)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e78.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePerineural Invasion (Present)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymphovascular Invasion (Absent)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymphovascular Invasion (Present)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Staging (pT1)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Staging (pT2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Staging (pT3)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Staging (pT4)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymph Node Stage (pN0)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymph Node Stage (pN1)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymph Node Stage (pN2)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTNM Stage (III)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTNM Stage (II)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTNM Stage (I)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMSI Status (MSS)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMSI Status (MSI)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe mean age of patients was 53.23\u0026thinsp;\u0026plusmn;\u0026thinsp;14.40 years. A male predominance was observed, with 69.0% of cases occurring in males and 26.2% in females.\u003c/p\u003e\u003cp\u003eLeft-sided tumors were more common (57.1%), followed by right-sided tumors (33.3%), and a small proportion of bilateral cases (4.8%). Among specific tumor locations, the most frequent sites were the sigmoid colon (26.2%) and rectum (23.8%), followed by the transverse colon (16.7%).\u003c/p\u003e\u003cp\u003eThe predominant histological type was adenocarcinoma (61.9%), followed by mucinous adenocarcinoma (26.2%) and signet ring cell carcinoma (7.1%). In terms of tumor differentiation, the majority were moderately differentiated (61.9%), while poorly differentiated tumors accounted for 28.6%.\u003c/p\u003e\u003cp\u003eIntratumoral lymphocytic response was absent in 73.8% of cases, while peritumoral lymphocytes were present in 95.2%. Perineural invasion was observed in 16.7% of cases, whereas lymphovascular invasion was seen in 54.8%. Tumor Staging and Lymph Node Involvement: pT3 tumors were the most common (64.3%), followed by pT4 (16.7%) and pT2 (11.9%). Lymph node involvement (pN1) was present in 38.1% of cases, while pN2 was noted in 26.2%. TNM Stage III was the most frequent (61.9%), followed by Stage II (21.4%) and Stage I (11.9%). MSS tumors were more prevalent (64.3%), whereas MSI tumors accounted for 28.6% of cases.\u003c/p\u003e\u003cp\u003eWe analyzed the clinicopathological characteristics of MSI and MSS colorectal carcinomas across multiple parameters, including age, gender, tumor laterality, size, histologic type, and grade (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparative Analysis of MSI and MSS Colorectal Carcinomas.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFeature\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSI (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMSS (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge Distribution\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Age\u0026thinsp;\u0026lt;\u0026thinsp;50 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.594\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Age\u0026thinsp;\u0026ge;\u0026thinsp;50 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e58.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e74.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.594\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex Distribution\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e75.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e70.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.787\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.787\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Laterality\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Right-sided\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.085\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Left-sided\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e70.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.085\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor Size Distribution\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Small (\u0026lt;\u0026thinsp;4 cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.894\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Medium (4\u0026ndash;6 cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e50.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.894\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Large (\u0026gt;\u0026thinsp;6 cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e48.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.894\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistologic Type\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Adenocarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e66.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Mucinous Adenocarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Signet-Ring Cell Carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistological Grade\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Well Differentiated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Moderately Differentiated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e58.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e70.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Poorly Differentiated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMSI colorectal carcinoma was more frequently observed in younger patients (\u0026lt;\u0026thinsp;50 years), accounting for 41.7% of cases, compared to 25.9% in MSS (p\u0026thinsp;=\u0026thinsp;0.594). Conversely, MSS tumors were more common in older patients (\u0026ge;\u0026thinsp;50 years), with a prevalence of 74.1%, whereas MSI tumors accounted for 58.3% in this age group. Males predominated in both groups, with a slightly higher proportion in MSI (75.0%) compared to MSS (70.4%), though the difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.787).\u003c/p\u003e\u003cp\u003eA notable difference was observed in tumor laterality. Right-sided tumors were significantly more frequent in MSI cases (50.0%) compared to MSS (29.6%), whereas left-sided tumors were predominant in MSS (70.4%) as opposed to MSI (33.3%) (p\u0026thinsp;=\u0026thinsp;0.085).\u003c/p\u003e\u003cp\u003eMSI and MSS tumors showed similar size distribution, with no significant differences. Medium-sized tumors (4\u0026ndash;6 cm) were the most common in both groups (MSI: 50.0%, MSS: 37.0%). Large tumors (\u0026gt;\u0026thinsp;6 cm) were slightly more frequent in MSS (48.1%) than MSI (41.7%), whereas small tumors (\u0026lt;\u0026thinsp;4 cm) were relatively uncommon in both groups (8.3% in MSI, 14.8% in MSS) (p\u0026thinsp;=\u0026thinsp;0.894).\u003c/p\u003e\u003cp\u003eThe predominant histologic type in both MSI and MSS cases was adenocarcinoma (66.7%), with no significant difference between the groups (p\u0026thinsp;=\u0026thinsp;0.012). Mucinous and signet-ring cell carcinomas were absent in both groups.\u003c/p\u003e\u003cp\u003eHistological grading revealed that poorly differentiated tumors were more frequent in MSI cases (41.7%) compared to MSS (22.2%), though this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.338). Moderately differentiated tumors were the most common in both MSI (58.3%) and MSS (70.4%) groups. Well-differentiated tumors were rare and only observed in MSS cases (7.4%).\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes the analysis of the pathological characteristics of MSI and MSS colorectal carcinoma based on immune response, histological subtype, invasion patterns, and tumor staging.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePathological Differences Between MSI and MSS Colorectal Carcinomas\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFeature\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMSI (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMSS (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntratumoral Lymphocytic Response\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Present\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.075\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Absent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e66.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e85.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.075\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePeritumoral Lymphocytic Response\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Present\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e100.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistologic Type\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Signet Ring Cell Carcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Adenocarcinoma (ACA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e66.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Mucinous Adenocarcinoma (MCA)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLymphovascular Invasion\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Present\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e63.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Absent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e58.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e37.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePerineural Invasion\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Present\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Absent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e83.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e85.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003epT (Pathological Tumor Stage)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- pT1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.420\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- pT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.420\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- pT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e91.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e55.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.420\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- pT4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.420\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003epN (Pathological Nodal Stage)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- pN0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.465\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- pN1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e41.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e40.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.465\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- pN2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.465\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTNM Stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Stage I\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.785\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Stage II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.785\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e- Stage III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e58.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.785\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA higher intratumoral lymphocytic response was observed in MSI cases (33.3%) compared to MSS (14.8%), though this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.075). In contrast, peritumoral lymphocytic response was universally present in all cases (100%), showing no distinction between MSI and MSS (p\u0026thinsp;=\u0026thinsp;1.000).\u003c/p\u003e\u003cp\u003eMucinous adenocarcinoma (MCA) was slightly more frequent in MSS cases (29.6% vs. 25.0% in MSI). However, signet ring cell carcinoma was more prevalent in MSI tumors (8.3% vs. 3.7%), and this difference was statistically significant (p\u0026thinsp;=\u0026thinsp;0.012).\u003c/p\u003e\u003cp\u003eLymphovascular invasion was more common in MSS (63.0% vs. 41.7% in MSI), though this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.317). Similarly, perineural invasion was observed at comparable frequencies in both groups (16.7% in MSI vs. 14.8% in MSS, p\u0026thinsp;=\u0026thinsp;0.088).\u003c/p\u003e\u003cp\u003eThe pT3 stage was predominant in MSI tumors (91.7%), whereas MSS tumors exhibited a greater proportion of pT4 cases (25.9%). However, the overall distribution of pT stages did not show statistical significance (p\u0026thinsp;=\u0026thinsp;0.420).\u003c/p\u003e\u003cp\u003eFor nodal involvement (pN stage), MSI cases were less likely to have advanced lymph node metastasis (pN2: 16.7%), compared to MSS cases (pN2: 29.6%), though this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.465).\u003c/p\u003e\u003cp\u003eA higher proportion of MSI tumors were Stage II (33.3%), whereas MSS tumors were predominantly Stage III (66.7%). Stage I cases were relatively uncommon in both groups (p\u0026thinsp;=\u0026thinsp;0.785).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study compared the clinicopathological characteristics of microsatellite instability-high (MSI-H) and microsatellite stable (MSS) colorectal carcinomas (CRCs), identifying significant differences in tumor location, histologic type, invasion patterns, tumor staging, and immune response. Our findings align with existing literature and reinforce the critical role of MSI testing in CRC management.\u003c/p\u003e\u003cp\u003eOur study found that MSI-H CRCs were predominantly located in the right (proximal) colon, whereas MSS CRCs were more frequent in the left-sided colon and rectum. This observation is consistent with findings from Patra et al. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], who reported that proximal colonic tumors had a higher frequency of MSI-H status, particularly in Indian patients [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Similarly, studies by Patil et al. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and Gandhi et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] also documented a higher incidence of MSI-H in right-sided CRCs, suggesting that MSI-H tumors arise through distinct molecular pathways compared to MSS tumors [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA significant association between MSI-H and mucinous adenocarcinoma was observed, with a higher proportion of mucinous and poorly differentiated tumors in MSI-H cases. This aligns with previous research by Kaur et al. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], who demonstrated that MSI-H tumors exhibited mucinous histology and were poorly differentiated compared to MSS tumors [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Furthermore, Jensen et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] and Carethers et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] reported that defective mismatch repair (dMMR) in MSI-H CRCs leads to an accumulation of mutations that drive mucinous differentiation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These histological differences are clinically relevant, as mucinous adenocarcinomas are associated with a different response to chemotherapy and overall prognosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur study found that MSI-H tumors exhibited a lower incidence of lymphovascular and perineural invasion compared to MSS tumors. This finding is consistent with Gelsomino et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], who reported that MSI-H CRCs are less likely to invade lymphatic and perineural structures due to their distinct molecular characteristics and robust immune microenvironment [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Lynch et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] further emphasized that tumors with MSI-H status often have a high mutational burden, leading to increased immune surveillance and lower rates of metastatic spread [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Additionally, Bellizzi et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] found that MSI-H tumors in rectal cancer were less likely to exhibit perineural invasion post-chemoradiation therapy, reinforcing the impact of MSI status on tumor progression [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur findings indicate a higher frequency of tumor-infiltrating lymphocytes (TILs) in MSI-H tumors, which is in agreement with previous studies. Gandhi et al. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] reported that TILs are a hallmark of MSI-H CRCs and contribute to their distinct immune profile [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Bashyam et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] further demonstrated that the immune response in MSI-H tumors is linked to mismatch repair (MMR) protein loss, which leads to increased antigen presentation and immune cell recruitment [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This immune microenvironment is a critical factor in the response of MSI-H tumors to immune checkpoint inhibitors (ICIs), such as PD-1 inhibitors, which have shown significant efficacy in MSI-H metastatic CRCs [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA key finding of our study was that MSI-H tumors were more frequently diagnosed at Stage II, whereas MSS tumors were more commonly Stage III and IV. This observation aligns with the findings of Gryfe et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], who reported that MSI-H CRCs are often diagnosed at an earlier stage, potentially due to their strong immune response limiting disease progression [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Yeole et al. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] also noted that patients with MSI-H tumors demonstrated better overall survival compared to MSS CRC patients, particularly in non-metastatic cases [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, while MSI-H tumors generally have a favorable prognosis in Stage II disease, their benefit in advanced stages remains controversial [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe distinct clinicopathological characteristics of MSI-H CRCs have important therapeutic implications. MSI-H tumors are less responsive to conventional 5-fluorouracil (5-FU)-based chemotherapy, as highlighted by Carethers et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], who found that MSI-H patients receiving 5-FU therapy did not show significant survival benefits compared to MSS patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Conversely, recent advancements in immunotherapy using PD-1 inhibitors (e.g., pembrolizumab, nivolumab) have shown remarkable efficacy in MSI-H CRCs, providing a strong rationale for MSI testing in treatment decision-making [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWhile this study provides valuable insights into the distinct features of MSI-H and MSS CRCs, certain limitations should be acknowledged. First, the retrospective design may introduce selection bias. Second, the sample size may not capture the full spectrum of MSI-associated clinicopathological variations. Future prospective studies with larger cohorts are needed to validate these findings and further explore the role of MSI in predicting treatment response.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlights the unique clinicopathological characteristics of MSI-H CRCs, including right-sided predominance, mucinous histology, poor differentiation, increased tumor-infiltrating lymphocytes, and lower rates of lymphovascular and perineural invasion. These features contribute to the distinct prognostic and therapeutic implications of MSI-H status, reinforcing the importance of MSI testing in guiding treatment decisions, particularly for immunotherapy eligibility. Future research should focus on optimizing treatment strategies for MSI-H tumors and further refining their prognostic value in CRC management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eCompeting Interests: The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Dr. Krishna Nair], [Dr. Divya Shetty] and [Dr. Anita Sharan]. The first draft of the manuscript was written by [Dr. Krishna Nair and Dr. Divya Shetty]. All authors read and approved the final manuscript.\u0026rdquo;\u003c/p\u003e\n\u003cp\u003eData Availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eEthics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethics Committee (IEC) for Biomedical and Health Research \u0026nbsp;(26/6/2021/No.DYP/IECBH/2021/137 ).\u003c/p\u003e\n\u003cp\u003eConsent to participate: Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003eConsent to publish: Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Fuchs HE, et al. Cancer statistics. 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ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumor mutational burden: a systematic review-based approach. Ann Oncol. 2019;30:1232\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/annonc/mdz116\u003c/span\u003e\u003cspan address=\"10.1093/annonc/mdz116\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYamashita K, Zhao M, Muto T, et al. The clinicopathological significance of microsatellite instability in colorectal cancer. Int J Clin Oncol. 2021;26:611\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10147-021-01850-0\u003c/span\u003e\u003cspan address=\"10.1007/s10147-021-01850-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGanesh K, Stadler ZK, Cercek A, et al. Immunotherapy in colorectal cancer: rationale, challenges and perspectives. Nat Rev Gastroenterol Hepatol. 2020;17:361\u0026ndash;75. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41575-020-0295\u003c/span\u003e\u003cspan address=\"10.1038/s41575-020-0295\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCohen R, Taieb J, Fiskum J, et al. Microsatellite instability in colorectal cancer: molecular basis, clinical impact, and therapeutic implications. J Clin Oncol. 2021;39:1756\u0026ndash;76. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/JCO.20.03363\u003c/span\u003e\u003cspan address=\"10.1200/JCO.20.03363\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatra T, Mandal S, Alam N, Murmu N. Clinicopathological trends of colorectal carcinoma patients in a tertiary cancer centre in Eastern India. Clin Epidemiol Glob Health. 2018;6:39\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatil PS, Saklani A, Gambhire P, Mehta S, Engineer R, De\u0026rsquo;Souza A, et al. Colorectal cancer in India: an audit from a tertiary center in a low prevalence area. Indian J Surg Oncol. 2017;8:484\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGandhi JS, Goswami M, Sharma A, Tanwar P, Gupta G, Gupta N, et al. Clinical impact of mismatch repair protein testing on outcome of early staged colorectal carcinomas. J Gastrointest Cancer. 2018;49:406\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGryfe R, Kim H, Hsieh ET, Aronson MD, Holowaty EJ, Bull SB, et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000;342:69\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaur G, Masoud A, Raihan N, Radzi M, Khamizar W, Kam LS. Mismatch repair genes expression defects \u0026amp; association with clinicopathological characteristics in colorectal carcinoma. Indian J Med Res. 2011;134:186.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJensen SA, Vainer B, Kruh\u0026oslash;ffer M, S\u0026oslash;rensen JB. Microsatellite instability in colorectal cancer and association with thymidylate synthase and dihydropyrimidine dehydrogenase expression. BMC Cancer. 2009;9:1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarethers JM, Smith EJ, Behling CA, Nguyen L, Tajima A, Doctolero RT. Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology. 2004;126:394\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGelsomino F, Barbolini M, Spallanzani A, Pugliese G, Cascinu S. The evolving role of microsatellite instability in colorectal cancer: a review. Cancer Treat Rev. 2016;51:19\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR. Review of the Lynch syndrome. Clin Genet. 2009;76:1\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBellizzi AM, Crowder CD, Marsh WL, Hampel H, Frankel WL. Mismatch repair status in rectal adenocarcinomas before and after chemoradiation. Lab Invest. 2010;90:137A.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBashyam MD, Kotapalli V, Raman R, Chaudhary AK, Yadav BK, Gowrishankar S, et al. Mismatch repair gene expression in Lynch syndrome cases in India. Mol Carcinog. 2015;54:1807\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYeole BB, Sunny L, Swaminathan R, Sankaranarayanan R, Parkin DM. Population-based survival from colorectal cancer in Mumbai, India. Eur J Cancer. 2001;37:1402\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Colorectal Neoplasms, Microsatellite Instability, Mismatch Repair Deficiency, Lymphatic Metastasis, Tumor Microenvironment","lastPublishedDoi":"10.21203/rs.3.rs-6591137/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6591137/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eMicrosatellite instability (MSI) is a key molecular marker influencing colorectal cancer (CRC) prognosis and treatment response. MSI-high (MSI-H) tumors exhibit distinct clinicopathological features compared to microsatellite stable (MSS) tumors. This study compares the characteristics of MSI-H and MSS CRCs to enhance clinical understanding and management.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective analysis was conducted on CRC cases with confirmed MSI and MSS status. Tumor specimens were evaluated for laterality, histologic type, grade, immune response, invasion patterns, and TNM staging. MSI status was determined using immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 proteins. Statistical analysis was performed using chi-square and t-tests, with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered significant.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eMSI-H tumors were predominantly right-sided (50%), with a higher frequency of mucinous histology (25%) and poor differentiation (41.7%). Intratumoral lymphocytic infiltration was higher in MSI-H tumors (33.3% vs. 14.8% in MSS, p\u0026thinsp;=\u0026thinsp;0.075). MSI-H tumors had lower lymphovascular invasion (41.7%) and were more frequently diagnosed at Stage II (33.3%), while MSS tumors were more common in Stage III (66.7%).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eMSI-H CRCs demonstrate right-sided predominance, mucinous histology, poor differentiation, increased immune infiltration, and lower lymphovascular invasion. These findings highlight the importance of MSI testing in prognosis and immunotherapy decisions.\u003c/p\u003e","manuscriptTitle":"A Comparative Study of MSI and MSS Colorectal Carcinomas: Histopathological and Clinical Findings from a Single-Center Retrospective Analysis in India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-08 09:41:14","doi":"10.21203/rs.3.rs-6591137/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0699587a-e653-4e92-b577-be314dd154ee","owner":[],"postedDate":"August 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-14T12:08:43+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-08 09:41:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6591137","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6591137","identity":"rs-6591137","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}