The Significance Of Mismatch Repair Protein In Colorectal Cancer And Its Relationship With BRAF^V600E Mutation

Objective: To examine the level of mismatch repair?MMR?protein expression in colorectal carcinoma?CRC?with the purpose of evaluating the relevance to clinical characteristics and BRAF^V600E mutation.Methods:.1 Recruit and select 723 pathologically confirmed CRC patients who were surgical treatment with non-preoperative chemoradiotherapy in The Fourth Hospital of Hebei Medical University from May 2015 to December 2016.Detect MMR proteins and BRAF^V600E protein expression of patients' tumour samples by immunohistochemical analys is.Determine as deficient mismatch repair?dMMR?with MLH1,PMS2,MSH2,MSH6 proteins depletion and as proficient mismatch repair?p MMR?otherwise.Besides,consider as BRAF^V600E gene mutation if BRAF^V600E protein depleted.2 Separate 723 patients into three groups based on MMR proteins expression and clinical pathology data:1)dMMR Sporadic Colorectal Cancer?dMMR SCRC?,2)p MMR Sporadic Colorectal Cancer?p MMR SCRC?,3)Hereditary nonpolyposis colorectal cance?HNPCC?.3 Statistical analysis : Chi-square test,logistic regression,Spearman rank correlation analysis and mean ± standard deviation?MSD?.Results:1 Approximately 13%?99/723?CRC samples were obviously MMR protein depletion,including 81 cases and 18 cases of HNPCC.The deletion rates of 4 kinds of MMR protein were 8.4%?61/723?MLH1 deletion,7.5%?55/723?PMS2,5.5%?40/723?MSH6 and 4.1%?30/723?MSH2.6.9% MLH1/PMS2?50/723?,4% MSH2/MSH6?29/723?and 0.5% MLH1/PMS2/ MSH6?4/723?were depletion of expression.The ratio of MLH1 or MLH1/ PMS2 in dMMR SCRC group?65.4%?was higher than in HNPCC group?50%?.These two groups were no significant difference?P>0.05?.However,The ratio of MSH2 or MSH2/MSH6 in dMMR SCRC group was less than in HNPCC group and had statistical significance?P<0.05?.2 dMMR SCRC group and p MMR SCRC group were significant difference?P<0.05?on onset age,differentiation,histological type,site,s ize,neurotrauma,lymphatic metastas is and TNM,and were no significant difference?P>0.05?on gender,invas ive depth,gross type and distant metastasis.multi-factor analys is showed that deficient mismatch-repair SCRC was closely related with the tumour site,differentiation and histological type?P<0.05?.3 dMMR SCRC group and p MMR SCRC group were significant difference?P<0.05?on onset age,but were no significant difference?P>0.05?on gender,site,size,histological type differentiation,TNM,neurotrauma,lymphatic metastasis,invasive depth,gross type and distant metastasis.4 ³.6%?26/723?CRC samples were BRAF^V600E mutation.8.6%?7/81?dMMR SCRC samples and 3%?19/624?p MMR SCRC were also BRAF^V600E mutation and these two groups were significant difference?P<0.05?.BRAF^V600E mutation and Deletion of MMR protein expression showed significant positive correlation?rs=0.095,P=0.012?.BRAF^V600E mutation ratio?9.4%,5/53?of MLH1 and MLH1/PMS2 samples were higher than BRAF^V600E mutation ratio of MLH1 expression samples?7.1%,2/28?but were no significant difference.Conclusions:1 lack of MMR proteins expression isn't commom in total CRC and MLH1 depletion is most frequent in dMMR CRC.Comparing with dMMR SCRC deficiency,MSH2 or MSH2/MSH6 deficiency in HNPCC patients are higher.2 MMR proteins expression depletion is a unique clinical and pathologic feature in SCRC.Tumor site,differentiation and histological type are independent risk factors for MMR deficiency.3 Age of onset in patients with HNPCC is more earlier.BRAF^V600E mutation rate in dMMR SCRC is high.The detection of MMR protein and BRAF^V600E can provide a reference for clinical individualized treatment and prognosis judgment,at the same time,improve the diagnosis rate of Lynch syndrome and simplify the screening process.