Assessment of Microsatellite Instability in Sporadic Colorectal Polyps: Implications for the Adenomacarcinoma Sequence

Objectives: The objective of this study was to assess the role of microsatellite instability (MSI), a molecular hallmark of defective DNA mismatch repair (MMR) in sporadic colorectal polyps using immunohistochemistry (for MLH1, MSH2, MSH6, and PMS2) as a surrogate marker for MMR protein expression. Additionally, we aimed to evaluate the applicability of the adenoma–carcinoma sequence in colorectal tumorigenesis, with the goal of identifying early molecular alterations that may facilitate timely intervention and prevention of invasive carcinoma. A cross-sectional study was conducted on 100 cas Materials And Methods: es of sporadic colorectal polyps diagnosed over a period of three years. Formalin-fixed, paraffin-embedded tissue blocks and corresponding hematoxylin and eosin-stained slides were retrieved and reviewed. Immunohistochemical analysis for MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed on all cases. The immunoreactivity of each marker was graded into five classes (Class 0–Class 4), with complete loss of nuclear staining interpreted as loss of protein expression, indicative of MSI. The study cohort comprised 8 Results: 4 males and 16 females (M:F = 5.25:1), with a mean age of 63.2 years (range: 11–85 years), indicating a male predominance. Histopathological sub typing revealed 82 adenomatous polyps, 17 hyperplastic polyps, and 1 juvenile polyp. Dysplasia was graded into three categories: Grade 0 (no dysplasia), Grade 1 (low-grade dysplasia), and Grade 2 (high-grade dysplasia). Statistical analysis was performed using Statistical Analysis: the Chi-square test in SPSS version 24. Loss of MMR protein expression was significantly associated with high-grade dysplasia (p = 0.004), suggesting a correlation between MSI and advanced neoplastic transformation. This study demonstrates a significant associatio Conclusion: n between MMR protein loss, detected by IHC, and high-grade dysplasia in sporadic colorectal polyps. The presence of MSI in both adenomatous and hyperplastic polyps underscores its potential utility as a biomarker for early detection and risk stratification in colorectal neoplasia.