Immunohistochemical Expression of MSH2 and MLH1 and Their Correlation with Histological Grades of Colorectal Carcinoma at Uganda Cancer Institute
Uganda
Abstract
Background: Colorectal Cancer (CRC) is a rising health challenge in Uganda. The mismatch repair (MMR) system, particularly MSH2 and MLH1, plays a critical role in maintaining genomic stability; defects contribute to CRC development. Immunohistochemistry (IHC) is a cost-effective method for detecting MMR protein expression in CRC tissues and aids diagnosis and treatment.
Study design
The study was a retrospective cross-sectional design
Objectives: To determine the immunohistochemical expression of MSH2 and MLH1 in archived CRC tissue blocks at the Uganda Cancer Institute (UCI) and to assess their correlation with tumor histological grades.
Methods: A retrospective analysis of 41 CRC tissue blocks collected from August 2017 to June 2023 was conducted using IHC. Histologically confirmed tissue sections were immunostained with MLH1 and MSH2 antibodies. Histological grading and IHC scoring were blinded performed on deferent dates and with different identifiers to avoid observers bias Spearman’s correlation assessed relationships between protein expression and tumor differentiation.
Results: MSH2 was expressed in 95% of tissue blocks and MLH1 in 92.7%. Loss of MSH2 and MLH1 occurred in 5% and 7.3% of cases, respectively. Most tumors were well differentiated (58.5%), followed by moderately (24.4%) and poorly differentiated (17.1%). There was no significant correlation between MSH2 expression and CRC grades (p = 0.151). MLH1 expression showed a positive correlation with poorly differentiated tumors (rho = 0.414, p = 0.007).
Conclusion: MSH2 and MLH1 expression was largely retained in this cohort of colorectal cancer cases at UCI, suggesting that most tumours were MMR proficient. Although MLH1 expression demonstrated a statistically significant correlation with poor differentiation, this pattern contradicts the loss of function biology of MLH1 and should therefore be interpreted with caution. The observed relationship is preliminary and requires validation using larger cohorts, molecular MSI testing, and more rigorous pathological review processes.