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Expression Of HMLH1,hMSH2 And HMSH6 In Young And Middle-aged Patients Withsporadic Colorectal Cancer And Its Effect On Prognosis

Posted on:2019-11-28Degree:MasterType:Thesis
Country:ChinaCandidate:Z H ZhengFull Text:PDF
GTID:2404330545954898Subject:Internal Medicine
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Background and ObiectivesColorectal cancer is one of the most common malignant tumors,with the morbidity and mortality being ranked the third and fourth places among the tumor patients worldwide respectively.Sporadic colorectal carcinoma accounts for about95%of the total number of colorectal cancer.Its occurrence and development is a multi-factor,Multi-step complicated process.Approximately 85%of SCCs are formed due to chromosomal aberrations,and about 10%-15%of SCC are caused by negative expression of mismatch repair proteins.In 1993,Lothe et al.proposed a new way of causing SCC-mismatch repair pathway.The basic principle is that the MMR gene ensures the high fidelity of gene duplication.When a mutation in MMR results in a loss of MMR function in the body,some of the mutated oncogenes or tumor suppressor genes rapidly accumulate in the body,causing tumors to develop.In this pathway,three MMR genes,hMLH1,hMSH2 and hMSH6,play a major role.The negative expression of MMR protein is highly predictive of the presence of MMR dysfunction.In recent years,the incidence of young and middle-aged patients with SCC has significantly increased,and its early detection and diagnosis becomes the hot spots of current cancer research.However,MMR in young and middle-aged SCC is rarely studied.The role of MMR in the development of young and middle-aged SCC needs to be further revealed.Based on this,we intend to investigate the e xpression of hMLH1,hMSH2 and hMSH6 in 96 cases of young and middle-aged SCC patients and their effects on prognosis,in order to provide the basis for the diagnosis and treatment of middle-aged and young patients with SCC.Materials and Methods1 Study subjectsA total of 96 paraffin-embedded specimens of pathological SCC were collected from January 2009 to January 2012 in the Second Affiliated Hospital of Zhengzhou University.2 Experimental methodsImmunohistochemistry was used to determine the expression of hMLH1,hMSH2 and hMSH6 in patients.3 Follow-upThe postoperative patients were followed up every three months,the follow-up time was 17-60 months,and the end date for the follow-up was February 2017.4 Statistical methodsData were analyzed by using SPSS 21.0 software.count data were compared using?~2 test.Kaplan-Meier analysis of survival time curve,Cox proportional hazard model for univariate and multivariate analysis,P<0.05 was considered statistically significant.Results1 The expressions of hMLH1?hMSH2?hMSH6The negative expression rate of MMR protein was 28.1%.The negative expression rate of hMLH1 was 20.8%(20/96).The negative expression rate of hMSH2 was 8.3%(8/96).The negative expression rate of hMSH6 was 7.3%(7/96).2 The relationship between MMR expression and clinicopathological features in young and middle-aged patients with SCCCompared with the group of proficient mismatch repair(pMMR),patients in the group of deficient mismatch repair(dMMR)were found more often in stage II,right colon,tumor diameter?5cm,ulcerative and infiltrative patients,and more difficult to lymph node metastasis.3 Effect of the expression status of MMR on Prognosis of the Middle and Young SCC PatientsFive-year disease-free survival and disease-free survival in the dMMR group were significantly higher than those in the pMMR group(?~2=8.955,P=0.003).The five-year overall survival and overall survival of the dMMR group were significantly higher than those of the pMMR group?~2=12.009,P=0.001).Univariate and multivariate analysis showed that MMR status was an independent factor influencing disease-free survival and overall survival(P<0.05).Conclusions1?MMR deletion in young and middle-aged patients with SCC is more common in patients with stage II,right colon,tumor diameter?5 cm,ulcerative and infiltrating.The deletion MMR group was more difficult to occur lymph node metastasis.2?The prognosis of the deletion MMR group was better than that of the normal MMR group.3?MMR status is an indepe ndent factor affecting the prognosis of patients with SCC.
Keywords/Search Tags:Mismatch repairprotein, Colorectal carcinoma, Pathological characteristics, Prognosis
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