Relationship Among HPV16 Infection And Expression Of HTERT, P21～(waf1), Ki67 In Cervical Intraepithelial Neoplasias And Squamous Cell Carcinomas Of Cervix Uteri

Objective To investigate the relationship among human papillomavirus(HPV)16 infection and expression of telomerase catalytic protein subunit(hTERT), tumor suppressor gene p21waf1,proliferation antigen Ki67 in cervicalintraepithelial neoplasias(CIN) and squamous cell carcinomas(SCC) of cervixuteri and its significance.Method Tissue microarray combined with In Situ Hybridation(ISH) andimmunohistochemical staining (EliVisionTM plus method) was used to detectthe expression of HPV16 RNA, hTERT, Ki67 and p21Waf1 protein in all 130cases ofnormal cervical tissue and CIN and SCC of the cervix uteri.Results 1) The positive rate of HPV16 hibridization signals in CINⅡ,CINIII,In situ carcinoma and invasive SCC were all significantly higher thanin normal cervical tissue(all P<0.05), and was also higher in SCC than in CIN(χ2=5.670,p=0.017). 2) The rate of positive expressionof hTERT protein inSCC/ In situ carcinoma /CINIII/ CINII were all significantly higher than innormal cervical tissue(all P<0.05) and was also significantly higher in SCC thanin In situ carcinoma and in CIN cases(χ2=18.870,p=0.000；χ2=66.390,P=0.000).There was a significant difference among CINI, CINII and CINIII(χ2=30.468,p=0.000). 3) The positive expression of p21 Waf1protein inSCC was significantly lower than in normal cervical tissue(P<0.05), but nosignificant differences between in SCC and in CIN(P>0.05).Also there was nosignificant difference among CINI, CINII and CINIII(P>0.05). 4)Ki67 showedstepwise high expression with increase severity in the histological grading of 3山西医科大学硕士学位论文cervical lensions(P<0.05). 5) The positive rate of HPV16 showed positivecorrelation to the expression of hTERT(P<0.05, r=0.339) and negativecorrelation to the expression of p21waf1(P<0.05, r=-0.337), but no relation toincreased cell proliferation(Ki67) (P>0.05). hTERT expression showed negativecorrelation to p21waf1 expression (P<0.05, r=-0.248), while showed positivecorrelation to Ki67 expression (P<0.05,r=0.398).There was negative correlationbetweenexpression of p21Waf1 and Ki67 (P<0.05,r=-0.446).Conclusion The results suggest that in tissues of CIN and SCC changes inhTERT, p21waf1 and Ki67 expression may be associated with HPV16 infectionand they interact with each other,which can influent the progression of CIN andcarcinogenesis of SCC.These biomarkers may be analyzed comprehensively torevealed the detailed mechanism which HPV16 participate in malignanttransformation and to provide some information on the diagnosis of patientswith high risk of malignant progression. Tissue microarray is an efficientplatform for high-throughput analysis of genes and their expression products ininvestigations.