Abstract:
Introduction
Colorectal carcinoma (CRC) is a major health problem worldwide and is one of the top causes of cancer
deaths. Defects in DNA mismatch repair (MMR) are responsible for a few cases of CRC, and the defect mainly
involves MLH1 and MSH2, which leads to microsatellite instability (MSI). Finding MMR deficiency is
important for predicting outcomes, screening for hereditary conditions like Lynch syndrome, and choosing
treatments such as immune checkpoint inhibitors. However, there is limited data on MMR protein
expression and its clinical associations in Indian patients. The objective of this study was to evaluate the
immunohistochemical expression of mismatch proteins MLH1 and MSH2 in colorectal carcinoma, and to
correlate MLH1 and MSH2 expression with clinicopathological parameters such as age, gender, tumor site,
histological type of tumor, and histological grade.
Materials and methods
This retrospective cross-sectional study included 45 histologically confirmed cases of CRC.
Immunohistochemical staining for MLH1 and MSH2 was performed on formalin-fixed, paraffin-embedded
tissue sections. Complete absence of nuclear staining in tumor cells, with intact internal controls, was
interpreted as loss of expression, indicating MMR deficiency and MSI. Retained expression of both proteins
was interpreted as MMR-proficient based on MLH1 and MSH2 expression, although complete assessment of
microsatellite instability ideally requires evaluation of all four mismatch repair proteins (MLH1, MSH2,
MSH6, and PMS2). Statistical analysis was performed to determine correlations with clinicopathological
variables such as age, gender, tumor site, histological type, and histological grade.
Results
The mean patient age was 56 ± 14 years. The majority of patients (n=27, 60%) were female. The colon was the
most common tumor site (n=25, 55.6%), and conventional adenocarcinoma was the main type (n=44, 97.8%).
Most tumors were moderately differentiated adenocarcinomas, comprising 35 (77.8%) patients. Overall, 21
patients (46.7%) were classified as MSI (MMR-deficient), while 24 (53.3%) were MSS (MMR-proficient).
MLH1 loss occurred in 19 (42.2%) patients, and MSH2 loss in nine (20%). MLH1 loss was significantly linked
to patients under 50 years of age (p = 0.009). MSH2 expression did not show a significant correlation with
clinical or pathological factors.
Conclusion
Many CRC cases in this study showed loss of MLH1 and/or MSH2, which suggests MMR deficiency and MSI.
MLH1 loss was closely linked to early-onset CRC and may point to a hereditary risk. Regular testing for MMR
proteins can help with diagnosis, screening for Lynch syndrome, and choosing the best treatment
