The Correlation between Tumour Location, Clinicopathological Characteristics and Mismatch Repair Protein (MMR) Status of Colorectal Cancer In Egyptian Patients

Abstract

Background: Colorectal cancer (CRC) is considered one of the most common cancers worldwide. By the year of 2035, it is predicted that there will be a dramatic rise of colonic and rectal cancers of 60% and 71.5% respectively. It has been reported that microsatellite instability (MSI) is a genetic target in hereditary nonpolyposis colorectal cancer cases however recent studies have shown that it is also implicated in the development of sporadic cases. MSI/MMR mutations can stimulate tumourigenesis by inactivating tumour suppressor genes and cases with high or deficient MMR (dMMR) have shown a better clinical outcome and response to programmed cell death 1 (PD-1) inhibitors in many studies. Furthermore, right and left sided colon cancers have different clinicopathological features and may display a different MMR status. Aim of the work: This work aimed to examine immunohistochemical expression of MMR proteins in colorectal tumours of Egyptian patients and their correlation with the age, sex, tumour grade, histological type and TNM stage to implicate possible therapeutic and prognostic potential. Material and Methods: This retrospective study was conducted on 409 cases of archived, formalin fixed paraffin embedded tissue blocks and immunohistochemical staining was performed using monoclonal antibodies against (MLH1, PMS2, MSH2 and MSH6). Results: MMR protein expression revealed intact expression (MMR-proficient status) in (84.4%) of the cases while (15.6%) of the cases showed lost protein expression. MMR protein loss was seen more frequently in patients with right side colon cancer compared to left side counterparts and this was statistically highly significant (p=0.001*). MLH1/PMS2 loss was the most frequent pattern while MSH2/MSH6 loss was less frequent. Moreover, a statistically significant correlation was demonstrated between loss of MLH1 and PMS2 among right-side tumours, while left-side CRC tumours revealed obvious loss MSH2 and MSH6. In regards to age and gender, a statistically significant correlation was seen regarding loss of MSH2 (p=0.008*) and MSH6 (p=0.002*). In thirty-eight cases, PMS2 was lost and showed a positive correlation regarding grade (p=0.045*). These results have shown the difference in MMR status of right and left sided colorectal cancers and the potential prognostic and therapeutic impact. Conclusion: The frequency of mismatch repair deficiency (dMMR) status in this cohort study carried on Egyptians’ CRC cases was 15.6%. It showed varying expression in right sided CRC in comparison to Left sided ones. The different biological factors regarding right and left sided colonic cancers may be used to identify cases who needs screening and further management.