TÌNH TRẠNG ĐỘT BIẾN BRAF V600E Ở BỆNH NHÂN UNG THƯ ĐẠI TRỰC TRÀNG DMMR TẠI BỆNH VIỆN BÌNH DÂN TỪ THÁNG 05/2021 ĐẾN THÁNG 10/2022

Abstract

OCTOBER 2022

Background: Colorectal cancer is the leading cause of morbidity and mortality worldwide while Lynch Syndrome (LS) being the most common inherited predisposition syndrome. Screening for LS includes testing for microsatellite instability status (MSI) or the expression of four mismatch repair (MMR) genes: MLH1, MSH2, MSH6 and PMS2 that guiding for analysing germline mutations. Recently, BRAF V600E mutation testing has become routine in the management of colorectal cancer patients because it is more technical available and more cost benefit for eliminating MLH(-) cases due to epigenetic changes. This study initially investigated the frequency of the BRAF V600E mutation in patients lossing expression of one or more MMR genes, which causes a phenotype called dMMR - deficient DNA mismatch repair. The results suggest the proportion of cases requiring germline genetic testing to diagnose LS, thence preparing resources and refining the most appropriate approach to manage LS for Vietnamese population. Objective: To investigate the proportion of BRAF V600E mutation in colorectal cancer patients with dMMR, and to analyse the correlation between BRAF V600E mutation status and a number of clinicopathological characteristics. Methods: 70 FFPE tissue samples of patients diagnosed colorectal cancer stored at the Department of Pathology, Binh Dan Hospital with immunohistochemical staining results of MLH1, PMS2, MSH2, MSH6 are dMMR from May 2021 to October 2022 were accepted into the study. The BRAF V600E mutation was detected using PCR techniques. Clinical and laboratory characteristics data were collected from medical records. Results: The prevalence of BRAF V600E mutation in colorectal cancer patients with dMMR features was 16%. No association was noted between BRAF V600E and both clinical features and tumor characteristics. The rate of dMMR MLH1(-) colorectal cancer is 47%, 97% of which are accompanied by loss of PMS2 expression and 100% of cases carrying the BRAF V600E mutation are MLH1(-)/PMS2(-). In the dMMR group without loss of MLH1 expression, 80% of cases carrying the BRAF V600E mutation were PMS2(-) and the proportion carrying the BRAF V600E mutation was significantly different between subgroups. Conclusion: The prevalence of BRAF V600E was 16% in the dMMR population. In the MLH1(-) subgroup, 100% of BRAF V600E carriers were PMS2(-). The use of BRAF V600E as a Lynch Syndrome screening tool in MLH1(-) cases is feasible.