The Expression And Significance Of Mismatch Repair Proteins MSH2 And MSH6 In Cervical Intraepithelial Neoplasia And Cervical Cancer

Objective:Mismatch repair genes are the protective genes of the cells, the main function of them is correcting base mismatch errors that occur during cells replication, they also play a crucial role in maintain the integrity of the DNA replication and human genome stability.The mismatch of genes could increase cell genomes’ instability, which may lead to a series of target genes changes, such as cell growth, differentiation, apoptosis and cancer metastasis, and finally induce a variety of the occurrence and metastasis of tumors. While mismatch repair proteins MSH2 and MSH6 are two important participants in the mismatch repair process, for the occurrence and development process of cervical cancer, them may also play a corresponding role in it. Therefore, the present study is to check the expression of mismatch repair proteins MSH2 and MSH6 in cervical intraepithelial neoplasia(CIN)and cervical squamous cell carcinoma(CSCC) tissues, and preliminary discuss the relations of the two proteins to the occurrence and development of cervical cancer.Looking forward to further improve the pathogenesis of cervical cancer, and looking for molecular markers to predict the progression of cervical intraepithelial neoplasia.Methods:1. Randomly collected cervical tissue specimens from October 2010 to June 2015 who inspected or treated in Shanxi Medical University Second Hospital of obstetrics and gynecology, included 23 cases of normal cervical tissues, cervical low-grade squamous intraepithelial lesions(LSIL) tissues 22 cases, cervical high-grade squamous intraepithelial lesions(HSIL) tissues 41 cases, and 63 cases of CSCC tissue samples. All specimens before we got have no other related treatment such as surgery, radiotherapy, chemotherapy, and no concurrent endocrine system disease, autoimmune diseases or other tumors combined, and all cases had integrity clinical datas.2. Used immunohistochemical SP method to detect the expression level of mismatch repair proteins MSH2 and MSH6 in CIN and CSCC tissues, the positive expression of both proteins were mainly located in the nucleus. Used diversion hybrid gene chip method to detect the infection of high-risk human HPV(HR- HPV) in the organizations.3. Used SPSS 19.0 software for statistical analysis. Grouped according to the pathological results, the comparison rate between groups use chi-square test and Fisher’s exact test, two-two compared use LSD-t test, correlation analysis used Spearman rank correlation. With P < 0.05 was considered statistically significant.Results:1. The positive expression rate of mismatch repair proteins MSH2 and MSH6 in normal cervical tissues, cervical LSIL, cervical HSIL and CSCC tissues were increased gradually. The expression of MSH2 in these groups in order was 21.74%(5/23),27.27%(6/22), 63.41%(26/41)and 66.67%(42/63), MSH6 in order was 26.08%(6/23), 31.82%(7/22), 65.85%(27/41),73.02%(46/63), the two proteins differences expression were statistically significant in both groups(P<0.05).2. The expression of MSH2 and MSH6 in FIGO clinical stage, age, tumor size and lymph node metastasis had no statistical significant difference(P>0.05), but were associated with the pathologic differentiation degree of CSCC, the lower the degree of differentiation, the higher the positive expression rate of the proteins, and the differences were statistically significant(P<0.05).3. Through Spearman correlation analysis, the positive expression of mismatch repair proteins MSH2 and MSH6 in CIN and CSCC tissues showed a significant positive correlation,the correlation coefficient rs was 0.757.4. With the increase of cervical lesion’s level, HR-HPV infection rate was higher, the difference was statistically significant(P<0.05); and HR-HPV infection rate was positively correlation with the expression of MMR MSH2 and MSH6 proteins, correlation coefficient rs were 0.299 and 0.363 respectively.Conclusions:The expression of mismatch repair proteins MSH2 and MSH6 were increased with the rising of cervical tissue lesion’s level, and the expression of the two factors showed a positive correlation with the infection of HR-HPV, showed that two kinds of proteins were closely related to the occurrence and development of cervical cancer.