The Effect Of Mismatch Repair/microsatellite Instability On Chemotherapy Sensitivity And Prognosis Of Advanced Colorectal Cancer

Backgroud and objectives:Colorectal carcinoma(CRC)is a common malignant tumor of the digestive tract.The incidence and mortality of colorectal cancer are ranked in the forefront of digestive system tumors.Colorectal cancer can be divided into polypoid,stenosis and ulcerative type according to the pathological tissue.Colorectal cancer has a high recurrence rate and a high mortality rate.Moreover,it often appears resistance to chemotherapy and insensitivity to radiotherapy in clinical treatment,resulting in poor clinical outcomes and poor prognosis.At present,the five year survival rate of colorectal cancer in China remains only about 60%.Even if a radical resection was performed,the rate of recurrence was still 20%-50%.Therefore,colorectal cancer has always been one of the most difficult problems in the oncology department.However,the specific pathogenesis of colorectal cancer is not very clear.The cancer epidemiological survey found that high fat diet may be an important risk factor for increasing the incidence of colorectal cancer.In addition to the external environmental factors,the inherent genetic genes also have a certain impact on the pathogenesis and progress of colorectal cancer.Mismatch repair is a self repair process of the body,mainly through the DNA mismatch repair(MMR)gene to repair the base mismatch sequence occurring during DNA replication.Therefore,the MMR gene plays a very important role in maintaining the stability of the genome.At present,6 mismatch repair genes have been cloned in human cells,including MSH2,MLH1,HMSH3,MSH6,PMSl,and PMS2.MMR defects will lead to the loss of mismatch repair function after replication,the cell spontaneous mutation frequency increased,namely microsatellite instability(MSI),2 or more than 2 sites of microsatellite instability is highly unstable(MSI-H);1 loci instability microsatellite instability(MSI-L);no loci for microsatellite instability(MSS)stability.It has been found that microsatellite instability has an important impact on chemotherapy sensitivity and prognosis of colorectal cancer.However,most of these studies are focused on patients with stage II and III colorectal cancer.Microsatellite instability is relatively rare for chemotherapy sensitivity and prognosis in patients with advanced colon cancer.For this purpose,we used immunohistochemical method to detect microsatellite instability in patients with advanced colorectal cancer,and analyzed its effect on chemosensitivity and prognosis of patients with advanced colon cancer.Methods:From December 2009 to December 2016,181 cases of colorectal cancer were treated in the Affiliated Hospital of Yangzhou University.All cases were diagnosed as stage IV colorectal cancer by histopathology,CT,MRI,and B ultrasonic examination,and all received first-line chemotherapy based on oxaliplatin combined with 5-FU.All cases of primary tumor tissues were collected.The expression of MLH1,PMS2,MSH2 and MSH6 protein was detected by immunohistochemical method.The relationship between the expression and the sensitivity and prognosis of chemotherapy was analyzed.Results:A total of 181 patients with advanced colorectal cancer were included in this study,including 96 males and 85 females.There were 76 cases less than 60 years old,105 cases were greater than or equal to 60 years old.There were 68 cases of low differentiation,113 cases of moderately high differentiation.There were 86 cases in the right half(including ascending colon,transverse colon,hepatic flexure),and left half(including rectum,sigmoid colon,descending colon and splenic flexure)in 95 cases.There were 11 cases of colorectal cancer with single metastasis and 170 cases of multiple metastases.In addition to lesion sites,there was no significant difference in other clinical characteristics between group MSI and group MSS(P>0.05).In the tumor tissues of 181 patients with advanced colorectal cancer,18 cases of immunohistochemical detection were dMMR,that is,group MSI,accounting for 9.9%,and 163 cases of immunohistochemical detection were pMMR,that is,group MSS,accounting for 90.1%.The multifactor COX regression analysis was used to analyze the follow-up data.There was no statistical difference in the distribution of OS in the MSI group and the MSS group(P = 0.21).All patients with advanced colorectal cancer were treated with first-line FOLFOX or XELOX chemotherapy.In group MSI,2 cases were partial remission,10 cases were stable,6 cases were progressive,the total effective rate was 11.1%and the disease control rate was 66.7%.In group MSS,14 cases were partial remission,54 cases were stable and 95 were progressive,the total effective rate was 8.6%,the rate of disease control was 41.7%,and the total effective rate of group two was not statistically significant,(?2 = 0.13,P = 0.72),but the rate of disease control in group MSI was significantly higher than that in group MSS(?2 = 4.09,P = 0.04).In addition,no complete remission occurred in this study.Conclusion:The microsatellite instability was not related to the total survival time of the patients with advanced colorectal cancer,and was positively correlated with the rate of disease control.Therefore,it is necessary to carry out microsatellite detection in the treatment of colorectal cancer patients.