细胞凋亡调节与宫颈癌发生

The Relationship between Apoptotic Regulation and Cervical Carcinogenesis

目的:探讨子宫颈癌发生中影响细胞凋亡的调节因素。方法:检测对象为194例经福尔马林固定石蜡包埋的手术切除标本,包括上皮内瘤样病变(CIN)78例犤其中重度非典型增生(SD)41例;原位癌(CIS)37例犦早期浸润癌(MIC)35例;大细胞非角化型浸润癌(IC)40例及正常宫颈鳞状上皮(NE)41例。凋亡细胞的检出使用TDT-mediateddUTP-biotinnickendlabeling(TUNEL)方法;细胞凋亡相关基因蛋白p53、bcl-2、bax的表达采用单克隆抗体免疫组化ABC染色方法;HPV16、18型E6DNA感染使用PCR方法进行检测。结果:1)凋亡细胞标记率仅在CIN呈现有意义地进行性减少(P<0.01),癌变以后不再继续下降;2)在SD、CIS组,p53、bcl-2及bax基因蛋白的表达与TUNEL标记率呈现有意义地相关性变化(P<0.05);3)HPV16、18型E6DNA感染与凋亡细胞及相关基因蛋白表达未呈现相关性改变。结论:以上结果提示细胞凋亡的改变与宫颈癌发生的早期过程有关,p53、bcl-2、bax基因蛋白参与其调节,而HPV16、18型E6DNA感染与其未呈现直接的相关性。

Objective:To investigate the relationship between apoptosis with regulatory apoptotic proteins and human papillovirus(HPV)infection in cervical carcinogenesis.Methods:Samples of formalin-fixed,paraffin-embedded tissues were obtained from surgical resections in a total of194cases,among them78cases of intraepithelial neoplasia including41cases of severe dysplasia(SD);37cases of carcinoma in situ(CIS);35cases of microinvasive carcinoma (MIC);40cases of frank invasive large cell non-keratizing epidermoid carcinoma (IC)and41samples of normal cervical squamous epithelium(NE).TDT -mediated dUTP -biotin nick and la belling(TUNEL)method and monoclonal antibody immunohistochemical staining with ABC were re spec-tively performed to detect the apoptotic cells and the expression of regulatory apoptotic pro teins p53,bcl-2,bax.The infection of HPV types16,18was determined by PCR.Results:1)The TUNEL staining index was significantly decreased from NE to CIS(P<0.01).2)In SD and CIS,the expression of p53,bcl-2and bax proteins showed significantly correlative variation with the TUNEL staining index(P<0.01).3)No correlative variation was found in the infection of HPV types16,18and the expression of regulatory apoptotic proteins.Conclusion:These data sug-gest that the variation of apoptosis is associated with the early stage of the cervical carcinogenesis and p53,bcl-2,bax pro teins participate in its regulation,how ever,no infection of HPV type16,18is observed to have direct corre lation with the variation of apoptosis.