凋亡异常与人乳头瘤病毒感染在宫颈癌发生中的意义

目的探讨宫颈鳞癌发生过程中端粒酶活性异常和高危型人乳头瘤病毒(HPV)感染的意义,同时分析与细胞周期蛋白异常表达的关系。方法应用荧光原位杂交(FISH)、显色原位杂交(CISH)及免疫组织化学检测鳞癌及上皮内瘤变组织中人端粒酶逆转录酶(hTERC)基因、高危型HPV 16/18、31/33和细胞周期蛋白Rb、P16ink4a、CDK4和Ki67的表达,正常宫颈组织作为对照检测。结果鳞癌和上皮内瘤变中hTERC基因的扩增率和高危型HPV及Rb、P16ink4a、CDK4和Ki67的阳性表达明显高于正常宫颈,鳞癌中高危型HPV的感染与hTERC基因的扩增呈正相关;高级别上皮内瘤变hTERC基因的扩增率显著高于低级别;Rb与Ki-67的阳性表达呈正相关;CDK4阳性表达与鳞癌组织学分级呈正相关;HPV16/18的感染与脉管内瘤栓的形成有相关关系。结论宫颈鳞癌的发生与高危HPV的感染密切相关,且其感染可能导致hTERC基因的异常扩增,二者协同作用导致癌变;hTERC基因的扩增可作为预测癌前病变进展的因子之一;P16ink4a、CDK4、Ki67可作为辅助诊断宫颈癌前病变严重程度的参考指标。

Abnormal apoptosis and human papilloma virus infection in carcinogenesis of cervical carcinoma

Objective To investigate the impact of abnormal human telomerase activity and high-risk human papilloma virus（HPV） infection on the carcinogenesis of cervical carcinoma,and to analyze their correlation with abnormal expression of cyclin.Methods The expressions of human telomerase gene（hTERC）,high-risk HPV DNA 16/18,31/33 and cyclins（P16ink4a,CDK4,Rb,Ki67） in squamous cell carcinoma and cervical intraepithelial neoplasia（CIN） were detected using fluorescence in situ hybridization,chromogenic in situ hybridization and immunohistochemical assay,as were normal cervical tissues designed as control.Results There was a marked increase in the amplification of hTERC gene,expression of high-risk HPV,Rb,P16ink4a,CDK4 and Ki67 in squamous cell carcinoma and CIN as compared with normal controls.Infection of moderate-to-high-risk HPV in squamous cell carcinoma was positively correlated with hTERC gene expression.A significantly higher amplification of hTERC was presented in advanced squamous cell carcinoma than that in low-grade carcinoma.Rb was correlated with the positive expression of Ki-67.There was positive correlation between the positive expression of CDK4 and histopathologic grading of squamous cell carcinoma.Also revealed was the correlation between HPV16/18 infection and intravascular tumor embolus.Conclusion Development of cervical carcinoma is closely correlated with high-risk HPV infection.Synergistic actions from infection with high-risk HPV and the resulting hTERC gene abnormal amplification may lead to carcinogenesis.The amplification of hTERC gene may be used as a predictor for progression of cervical precancerous lesion,and P16ink4a,CDK4 and Ki67 may be used to indicate the severity of cervical precancerous lesion in adjunctive diagnosis.