Significance of Dna Mismatch Repair Genes and Microsatellite Instability in Colorectal Carcinoma in Ibadan, Nigeria

Background: Though the incidence of colorectal carcinoma (CRC) is relatively uncommon in Nigeria, compared to the developed countries, recent studies indicate an increasing trend. Our patients often present at an earlier age, which has important implications for the pathogenesis in Nigeria. MLH1, MSH2, MSH6, PMS2 are the commonly mutated MMR genes in descending order of frequency, with PMS1 and MLH3 mutations being very rare. This study attempts to determine the significance of microsatellite instability (MSI) in colorectal carcinogenesis using immunohistochemistry (IHC) for detection of defects of DNA mismatch repair gene (MMR) amongst cases diagnosed at University College Hospital (UCH) Ibadan, Nigeria. Methodology: Suitable consecutive CRC cases identified from UCH, Ibadan, Pathology Department, 2006 files were stained with MMR IHC antibody panel (MLH1, MSH2, MSH6, PMS2). Stained sections were reviewed for nuclear reactivity and graded according to staining intensity (weak +, moderate ++, strong +++, very strong ++++). Result: IHC was performed on 26 cases. The age range is 22-74 years with 9 cases <40 years. One case with no reactivity with any of the antibody was considered unsuitable. Two cases with only PMS2 nuclear reactivity but no reaction with other antibodies were considered equivocal. Five cases had no nuclear reactivity with single antibody: MLH1 (2); MSH2 (3); and one case had no nuclear reactivity with MLH1 & MSH2. These six cases included 3 cases aged 22, 27 and 32 years with tumors showing no nuclear reactivity for MSH2 and (MLH1 & MSH2) respectively. Conclusion: Though the number cases tested are small, the identification of the loss of MMR gene protein (MLH1 and MSH2) by IHC, indicating MSI, in a significant number of the 26 cases tested (23%), particularly young individuals, suggests that defects of DNA mismatch repair genes are important factors in colorectal carcinogenesis in Nigerians.