A Study Of Microsatellite Instability And Loss Of Heterozygosity In Cervical Cancer And Cervical Intraepithelial Neoplasia

Objective:1.To explore the relationship of loss of heterozygosity(LOH) and microsatellite instability(MSI) in the development of cervical cancer and cervical intraepithelial neoplasia.2.Explore the mismatch repair genes and the fragile histidine traid genes in the development of cervical cancer,thus provide the basis of the early detection and treatment in cervical cancer.Methods:MSIand LOH of 6 microsatellite markers D2S123,D4S43,D4S125,D3S1297,D3S4103,D3S1298 were detected in 60 cervical cancers and 50 cases of cervical intraepithelial neoplasia(CIN) and self normal cervix.Results: Compare the PCR products of tumor tissues and corresponding normal tissue DNA at the same time.If a particular allele in tumor tissue strip with non-tumor tissue compared with the corresponding article completely disappear or relative density of more than 50%reduction,the result is the LOH;if the tumor tissue compared with non-tumor tissue strip happened translocation or increased,the result is the MSI.1.The relationship of LOH and cervical cancer:Compared 60 cases of invasive cervical organization and its corresponding normal tissue,the positive rates were gradually increased with the degree of malignancy of cervical cancer. Except D4S125,significant differences were noted between FIGO stage of cervical cancer,between the well,the moderately and the poorly differentiated cervical carcinomas and between the invasive cervical cancer with lymphnode metastasis and those without lymphnode metastasis in regard to LOH(P＜0.05).2.The relationship of MSI and cervical cancer:Compared 60 cases of invasive cervical organization and its corresponding normal tissue,the positive rates were gradually increased with the degree of malignancy of cervical cancer. On D2S123,D3S4103,D3S1298,significant differences were noted betweenⅢ,Ⅳstage andⅠ,Ⅱstage of cervical cancer,between the well,the moderately and the poorly differentiated cervical carcinomas and between the invasive cervical cancer with lymphnode metastasis and those without lymphnode metastasis in regard to MSI(P＜0.05).3.The relationship of LOH and CIN:Except D4S43 and D4S125,significant differences were noted betweenⅠ,Ⅱstage andⅢstage of 50 cases of CIN (P＜0.05).4.The relationship of MSI and CIN:On D2S123,D3S4103 and D3S1298, significant differences were noted betweenⅠ,Ⅱstage andⅢstage of 50 cases of CIN(P＜0.05).5.The relationship of the mismatch repair genes and CIN and cervical cancer: At two loci D2S123 and D3S1298 with mismatch repair gene-related,the positive rate of MSI and LOH increase with its increased level,significant differences were noted between FIGO stage of cervical cancer,between the well,the moderately and the poorly differentiated cervical carcinomas and between the invasive cervical cancer with lymphnode metastasis and those without lymphnode metastasis in regard to LOH(P＜0.05).6.The relationship of the fragile histidine traid genes and CIN and cervical cancer:At one loci D3S4103 with the fragile histidine traid gene-related,the positive rate of MSI and LOH increase with its increased level,significant differences were noted between FIGO stage of cervical cancer,between the well,the moderately and the poorly differentiated cervical carcinomas and between the invasive cervical cancer with lymphnode metastasis and those without lymphnode metastasis in regard to LOH(P＜0.05). 1.6 loci with high LOH and MSI prompt that tumor-suppressor gene with the development of cervical cancer near these sites.2.Statistical significance was noted between LOH,MSI and clinical stage, pathological grade in cervical cancer,prompt that detected LOH and MSI in these regions can be used as important indicators with tumor malignant degree and prognosis.3.Statistical significance was noted between LOH,MSI and pathological grade in CIN,prompt that LOH and MSI was a later period event in the occurrence and development of CIN.4.Mutations of mismatch repair gene are an important reason for in tumor happened,its detection contribute to prognosis and early diagnosis of cervical cancer.5.The fragile histidine traid genes occurs mutation in many kinds of tumor,and we find it occurs on early lesions of cervix,so that it is an early case.