Analysis Of Clinical Features And Prognosis Of Colorectal Cancer Patients With Missing Expression Of DNA Mismatch Repair Protein

Objective:To investigate the clinical characteristics of colorectal cancer(CRC)patients with Mismatch Repair(MMR)protein deletion and to determine factors influencing disease free survival(DFS)and overall survival(OS).To analyze the relationship between different types of MMR protein loss and prognosis of patients.Methods:The clinicopathological data of colorectal cancer patients who were pathologically confirmed to have colorectal cancer and who underwent radical cancer excision surgery,specimen was analyzed by immunohistochemistry and MMR gene deletion was detected,from June 2012 to December 2014 in the Department of Oncology at the First Affiliated Hospital of Kunming Medical University,was collected and retrospectively analyzed.They were grouped according to the type of MMR protein deletion into hMLH1(MutL homologue 1),hMSH2(MutS homologues 2),hMSH6(MutS homologues 6)and hPMS2(Postmeiotic segregation increased 2).According to recurrence or metastasis,patients were divided into relapse or metastasis group and disease free survival group during follow-up.Patients were divided into death group and survival group according to whether the patient died.Results:1?In 158 patients with CRC with deletion of MMR protein on IHC,there were 89 males and 69 females with a male to female ratio of 1.29:1;the average age of onset was 58.33±13.23 years,and the median age at onset was 61 years.Among them,56(35.44%)patients were in the hMLHl protein deletion group,19(12.03%)patients were in the hMSH2 protein deletion group,17(10.76%)patients were in the hMSH6 protein deletion group,and 66(41.77%)patients were in the hPMS2 protein deletion group.2?In the hMLH1 protein deficiency group,preoperative serum tumor markers(carcinoembryonic antigen,CEA)was positive in 39(69.64%,P =0.003),35 patients underwent adjuvant chemotherapy(62.50%,P= 0.031),the difference was statistically significant.Among the hMSH2 protein deficiency group.17 cases(89.47%,P<0.01)were found in the rectum,and 18 patients(94.74%,P=0.022)needed adjuvant chemotherapy after surgery.Loss of hMSH6 Protein and loss of hPMS2 Protein were not correlated with sex,tumor site,tumor differentiation,preoperative serum tumor marker CEA,carbohydrate antigen 19-9(CA19-9),T Stage(depth of tumor infiltration),N staging(number of regional lymph node metastasis),neurovascular invasion and postoperative polyp recurrence(P>0.05).3?During the follow-up period,62(39.24%)of the 158 patients experienced recurrence and metastasis,41(25.95%)of them died,and their 3-year disease-free and overall survival rates were 60.76%and 74.05%,respectively.Group analysis showed that the 3-year disease-free survival rates of patients with hMLH1,hMSH2,hMSH6,and hPMS2 protein deletion groups were 67.91%,47.44%,64.72%,and 57.63%,respectively,and the mean DFS was 28.64±12.74 months,24.84±11.86 months,30.53±9.91 months and 25.94±13.56 months respectively.The Log-rank test suggested that the absence of different kinds of MMR proteins was not correlated with DFS(P=0.760);the 3-year overall survival rates of patients with hMLHl,hMSH2,hMSH6,and hPMS2 protein deletion groups were at 78.62%,52.63%,82.41%,and 74.26%,the mean OS was 32.30±8.23 months,31.05±6.92 months,34.00±5.49 and 31.85±8.76 months respectively.The Log-rank test suggested that the absence of different types of MMR protein was not related to OS(P=0.171).4?Univariate analysis showed that preoperative serum tumor markers CA19-9(P=0.008),T stage(P<0.001),Nstage(P<0.001),vascular tumor thrombus(P<0.001),nerve invasion(P=0.001)were the factors influencing DFS in CRC patients with MMR protein deletion.Multivariate logistic regression analysis showed that T stage(P<0.001,OR=2.90)and vascular tumor thrombus(P<0.001,OR=4.33)were independent risk factors affecting DFS,and postoperative polyp recurrence(P=0.018,OR=0.36)was a protective factor for relapse or metastasis.Univariate analysis showed that the risk factors of OS in CRC patients with MMR deletion were:T stage(P<0.001),Nstage(P<0.001),vascular tumor thrombus(P<0.001),nerve invasion(P=0.001),and multivariate logistic regression analysis showed T staging(P= 0.002,OR=2.52)and vascular tumor thrombus(P=0.001,OR=4.19)were independent risk factors affecting the OS,and postoperative polyp redistribution(P=0.003,OR=0.21)was a protective factor.Conclusions:1?In CRC patients with MMR protein deficiency,hPMS2 protein deletion was the highest and hMSH6 protein deletion was the lowest.2?The preoperative serum tumor marker CEA was significantly increased in patients with deletion of hMLHl protein.The tumors with hMSH2 protein loss occurred in the rectum,and the stage in patients with hMLHl and hMSH2 protein loss was higher postoperatively,needing adjuvant chemotherapy.3?There was no significant difference in three-year DFS and OS among hMLHl,hMSH2,hMSH6,and hPMS2 protein depletion groups.However,the DFS and OS of the hMSH2 protein depletion group were the shortest.4?T-stage,N-stage,vascular tumor emboli,and nerve invasion are risk factors affecting DFS and OS.Preoperative serum tumor marker CA19-9 is a risk factor affecting DFSof patients.T-stage and vascular tumor thrombus are independent risk factors affecting DFS and OS of patients.Recurrence of polyps after surgery is a protective factor.