Expression And Significance Of Mismatch Repair Genes HMSH6、hMSH2and P53in Sporadic Colorectal Carcinoma

Colorectal cancer (CRC) is one of the most common malignant tumors ofthe digestive system tumors, the incidence of colorectal cancer in Chinaranked fourth in the all malignant tumors, and its incidence is increasing yearby year. Recent epidemiological data showed that700thousand peoplethroughout the world suffer from CRC, accounting for9.4%of all new casesof cancers. Along with economic development, the improvement of livingstandards and changing lifestyles, the incidence of CRC will also be on arising trend.Colon cancer is found mostly in the middle-late stage，which more than80%of sporadic colorectal cancer is sporadic colorectal carcinoma,(SCC).Previous research has found that the occurrence and development ofcolon cancer ways mainly include two:(1) chromosomal instability,(CIN),which is given priority to oncogenes and tumor suppressor genes (2)microsatellite instability,(MSI),which is given priority to mismatch repairgenes,(MMR)[2]. Studies have shown that the MMR inactivation systemthrough two ways lead to the occurrence of tumor:①Microsatelliteinstability,which can indirectly caused the inactivation of tumor suppressorgenes or oncogene activation and the accurence of the cancer.②The MMRinactivation of the system can directly cause the oncogene activation andtumor suppressor gene inactivation,which eventually induced cancer[3]. TheMMR is an important member of DNA repair system, which is closely relatedto the onset of a variety of malignant tumors, especially closely related to theonset of colorectal cancer. The MMR genes are founded when people were inthe study of genetic non familial polyposis colorectal cancer, meanwhile, theMMR gene mutations are also associated with about15%of SCC. This studyselected hMSH2and hMSH6,which represented the way of MSI and P53gene,which was on behalf of the way of CIN. We use the immunohistochemical method to detect their expression in SCC, in order toinvestigate the clinical application value of P53and MMR in sporadiccolorectal cancer.Objective:To investigate the expression of hMSH2、hMSH6与P53in the SCC andthe relationship with the clinicopathological features in the SCC, which canprovide experimental basis for clinical treatments and diagnosis exceptprobing their roles in the appearance and development of SCC.Methods:Select60cases of patients who received surgical treatment came fromBaoding Central Hospital from January2010to December2012. All SCCpatients before surgery were not carried out any cancer treatment, includingradiation therapy and chemotherapy and all the specimens were confirmed bypathological examination after surgery and confirmed primary Sporadiccolorectal cancer, which are all adenocarcinoma, not concluding (familialadenomatous polyposis， FAP) and hereditary nonpolyposis colorectalcancer，HNPCC) and all patients，pathological information are complete. And60cases of normal colorectal tissues as the control group are apart fromcancer tissues at least5cm. To collecte the complete clinical data of60casesof SCC patients, including gender, age, height, TNM stage, clinical stage,histological grade and immunohistochemical pathology report and do acomplete record. At the same time, we check leak registration, The data wereanalyzed by using SPSS17.0statistical software, count data using X2test,Correlation using Spearman correlation analysis, α=0.05as tests, with P<0.05for the difference was statistical significant.Results：1. The expression of hMSH2in SCC and its correlation withclinicopathological features.The positive expression rate of hMSH2was38/60(63.3%),which wassignificantly increased in endometrial carcinoma tissues compared to that23/60(38.3%) in the normal tissue adjacent to carcinoma, the difference was statistically significant (P＜0.05)（X2=36.473，P＜0.05）.The expression of hMSH2was closely associated with tumor infiltrationdepth, tumor differentiation degree and lymph node metastasis (P＜0.05),which has nothing relationship with the patient’s age, sex and tumor size,tumor location.2. The expression of hMSH6in SCC and its correlation withclinicopathological featuresThe positive expression rate of hMSH6was33/60(55.0%),which wassignificantly increased in endometrial carcinoma tissues compared to that14/60(23.3%)in the normal tissue adjacent to carcinoma,the difference wasstatistically significant (P＜0.05)（X2=12.626，P＜0.05）.The expression of hMSH6was closely associated with tumor infiltrationdepth, tumor location (P＜0.05),which has nothing relationship with thepatient’s age, sex,tumor size and lymph node metastasis.3. The expression of P53in SCC and its correlation withclinicopathological featuresThe positive expression rate of P53was33/60(55.0%), which wassignificantly increased in endometrial carcinoma tissues compared to that5/60(8.33%) in the normal tissue adjacent to carcinoma,the difference wasstatistically significant (P＜0.05)（X2=30.193，P＜0.05）.The expression of P53was closely associated with tumor infiltrationdepth and lymph node metastasis(P＜0.05),which has nothing relationshipwith the patient’s age, sex,tumor size and tumor location4. The expression of hMSH2, hMSH6with P53in the correlationThe expression of hMSH2is positively correlated with hMSH6and P53.Conclusion:1. There was a high level protein expression in hMSH2, hMSH6and P53in the SCC, which may be involved in the formation and developmentof SCC. They also had a close relationship with the clinicopathologicalfeatures, which may be used as a indicator to judge tumor malignantdegree and prognosis. 2. P53protein was positively related with the expression of MMR protein,which indicates that there may be some kind of cooperative relationshipin the process of leading to the occurrence of SCC between them.