Relalionship Among HPV16 Infection and Expression of hTERT,P21~(warl),Ki67 in Cervical Intraepithelial Neoplasias and Squamous Cell Carcinomas of Cervix Uteri

To investigate the relationship among human papillomavirus(HPV)16 infection and expression of telomerase catalytic protein subunfit(hTERT),tumor suppressor gene P21wafl,proliferationantigen Ki67 in cervical intrepithelial neoplasias(CIN) and squmous cell carcinomas(SCC) of cervix uteri and their significance.Tissue microarray combined with in situ hybridation(ISH) and immunohistochemical staining(EliVisionTM plus method)was used to detect the expression of HPVI6RNA,hTERT,Ki67 and P2Iwaflprotein in all 130 cases of normal cervical tissue and CIN and SCC of the cervix uteri.The results are as follows.1)The positive rate of HPVI6 hybridization signals in CIN II,CINⅢ,in situ carcinoma and invasive SCC were all significantly higher than in normal cervical tissue(all P0.05),and was also higher in SCC than in CIN(χ2=5.670,P=0.017).2)The rate of positive expression of hTERT protein in SCC/ in situ carcinoma /CINIII/ CINII were all significantly higher than in normal cervical tissue(all P0.05) and was also significantly higher in SCC than in situ carcinoma and in CIN cases(χ2=18.870,P=0.000;χ2=66.390,P=0.000).There was significant difference among CINI,CINII and CINIII(χ2=30.468,P=0.000 ).3) The positive expression of P21wafl protein in SCC was significantly lower than in normal cervical tissue(P0.05),but no significant differences between in SCC and in CIN(P0.05).Also there was no significant difference among CINI,CINII and CINIII(P0.05).4)Ki67 showed stepwise high expression with increase severity in the histological grading of cervical lensions(P0.05).5) The positive rate of HPV16 showed,positive conelation to the expression of hTERT(P0.05,r=-0.339) and negative correlation to the expression of p2Iwafl(P0.05,r=-0.337),but no relation to increased cell proliferation(Ki67)(P0.05).hTERT expression showed negative correlation to P21waflexpression(P0.05,r=-0.248),while showed positive correlation to Ki67 expression(P0.05,r=0.398).There was negative correlation between expression of P21wafland Ki67(P0.05,r=-0.446).The resuts suggest that in tissues of CIN and SCC changes in hTERT,P21wafland Ki67 expression may be associated with HPV16 infection and they interact with each other,which can influent the progression of CIN and carcinogenesis of SCC.These biomarkers may be analyzed comprehensively to reveal the detailed mechanism which HPV16 participate in malignant transformation and to provide some information on the diagnosis of patients with high risk of malignant progression.Tissue microarray is an efficient platform for high-throughput analysis of genes and their expression products in investigtions.