The Relationship Between The High-frequency Microsatellite Instability Of Unmutated BRAF^V600E And The Clinicopathological Features Of Sporadic Colorectal Cancer

Objective Purpose Colorectal cancer(CRC)is one of the most malignant tumors that currently threaten the health of human beings.The study found that there are different molecular mechanisms of the occurrence and development of colorectal cancer,in which the mechanism of microsatellite-instability status(MSI)plays an important role.This article focuses on the relationship between the high-frequency microsatellite-instability(MSI-H)of unmutated BRAFV600 E and the clinicopathological features of sporadic colorectal cancer(SCRC)。Materials and Methods We collection of tumor tissue specimens of patients with sporadic colorectal cancer without complete neoadjuvant chemotherapy preoperatively from June 2016 to October 2017 in Qingdao Municipal Hospital Affiliated to Qingdao University.First,the tumor tissue samples of colorectal cancer patients meeting the inclusion criteria were made into paraffin sections.The expression of four mismatch repair proteins(MLH1,PMS2,MSH2,MSH6)is determined by immunohistochemistry(IHC).According to the current general standard: One or more mismatch repair proteins(MMRs)lacking in expression are thought to be microsatellite instability(MSI).There are two or more MMR protein expression deletion is called high frequency microsatellite instability(MSI –H).There is a lack of MMR protein expression called low frequency microsatellite instability(MSI-L)and on lacks of MMR protein expression was microsatellite stable(MSS).The mutation of BRAFV600 E in colorectal cancer samples of MSS / MSI-L and MSI-H was detected by immunohistochemistry(IHC)and analyze the correlation by statistical methods.We screen the non-mutated BRAFV600 E rectal cancer specimensand the clinical and collecte the pathological data of colorectal cancer patients.The mutations of BRAFV600 E in sporadic colorectal cancer specimens of MSS/MSI-L and MSI-H were detected by immunohistochemistry(IHC)and their correlations were analyzed.Among the non-mutant sporadic colorectal cancer patients in BRAFV600 E,43 patients(9.7%)showed colorectal cancer with MSI-H,and the colorectal cancer patients with MSS/MSI-L accounted for 401 cases(90.3%).The correlation between the MSI-H of non-mutated BRAFV600 E and clinicopathological features was analyzed by statistical methods.Results The number of patients with BRAFV600 E mutation was 29.The mutation rate of BRAFV600E was 6.1%.The positive samples of BRAFV600 E mutations in colorectal cancer of MSS/MSI-L group were 16 cases(3.8%),while the positive samples of BRAFV600 E mutation in MSI-H colorectal cancer were 13 patients(23.2%).The BRAFV600 E mutation rate of sporadic colorectal cancer in MSI-H group was significantly higher than that of MSS/MSI-L colorectal cancer BRAFV600 E group,and there was a significant difference between the two groups(P<0.05).The combined deletion status of MMR protein in MSI-H of unmutated BRAFV600 E is as follows : The combined deletion of MLH1 and PMS2 was 21 cases(48.4%);The combined deletion of MLH1 and MSH2 was 7 cases(16.3%);The combined deletion of MSH2 and MSH6 was 6(13.9%);The combined deletion of PMS2 and MSH2 was 2(4.7%);The combined deletion of PMS2 and MSH6 was 3 cases(7%);and the combined deletion of PMS2,MSH2 and MSH6 was 4 cases(9.3%).Wedidn’t find the joint deletion of MLH1,PMS2,MSH2 and MSH6 in this study.The comparetion between MSS / MSI-L sporadic colorectal cancer of unmutated BRAFV600 E and MSI-H sporadic colorectal cancer of unmutated BRAFV600 E were significant differences in age of onset,tumor location,degree of differentiation,clinical stage and P53 expression,mainly manifested in patients with sporadic colorectal cancer with negative BRAFV600 E mutation MSI-H,lower age of onset,lower degree of differentiation,more common in the ascending colon,earlier clinical stage,relatively low P53 mutation rate.However,there was no significant difference in the depth of invasion,gross tumor classification,histological type,nerve invasion,vascular invasion,tumor nodules.Conclusions There was a statistically significant difference in BRAFV600 E mutations between MSI-H and MSS/MSI-L groups;BRAFV600E unmutated MSI-H sporadic colorectal cancer patients have an earlier age of onset,earlier clinical stage,tumor differentiation,relatively poorly differentiated cancer is relatively common,P53 mutation rate is relatively low,the site of disease rise The colon is relatively common.