角化型外阴鳞癌与上皮内非瘤样变组织中DNA倍体及其与细胞增殖关系的研究

Relationship between DNA ploidy and cell proliferation of keratinizing vulvar squamous cell carcinomas and non-neoplastic epithelial disorders

目的:研究角化型外阴鳞癌(vulvarsquamous cell carcinomas,VSCCs)与外阴上皮内非瘤样变(non-neoplastic epithelial disor-ders,NNED)组织中DNA倍体及其与细胞增殖的关系,探讨异常增殖在外阴癌变中的作用。方法:采用图像分析方法检测21例角化型VSCCs、7例外阴上皮内瘤变(vulvar intra-epithelial neoplasia,VIN)和53例NNED组织细胞的DNA倍性,并采用免疫组化方法检测其增殖细胞核抗原(proliferating cell nuclearantigen,PCNA)的表达,9例正常外阴皮肤作对照。结果:从正常外阴皮肤、NNED、VIN到VSCCs组织,DNA指数(DNAindex,DI)和PCNA标记指数(PCNAlabeling index,LI)呈逐渐增高趋势,P=0.00。VSCCs组织中,DI和LI显著高于VIN、NNED和对照组,P<0.05。高分化癌患者的DI和LI显著低于中、低分化癌患者,P<0.05。正常外阴皮肤未检测出DNA非整倍体,VSCCs的非整倍体率38.1%,显著高于NNED和正常外阴皮肤组,P<0.05。在NNED中,非整倍体组的LI显著高于正常倍体组,P=0.00。结论:非整倍体出现导致遗传学不稳定可能是外阴良性疾病恶变的早期驱动力,检测NNED中的DNA倍性有助于判断其恶变潜在性。

OBJECTIVE： To study the relationship between DNA ploidy and cell proliferation of vulvar squamous cell carcinomas （ VSCCs ） and non-neoplastic epithelial disorders （NNED）, and to investigate the possible roles of proliferative changes in vulvar carcinogenesis. METHODS： Nine cases of normal vulvar skins, 53 cases of NNED, 7 cases of vulvar intraepithelial neoplasia （VIN） and 21 cases of keratinizing VSCCs were investigated by image analysis and immunohistochemistry to determine DNA content and the expression of proliferating cell nuclear antigen （PCNA）. RESULTS： The DNA index （DI） and the PCNA labeling index （LI） from normal vulvar skins, NNED, through VIN to VSCCs were significantly increased, P= 0.00. DI and LI were significantly higher in VSCCs than those in VIN, NNED and normal vulvar skins, respectively, P〈0.05. Signifi- cant correlations were found between DI and LI and the histopathologic grade of the cancer cells, P〈0.05. No control nor- mal vulvar skins exhibited DNA aneuploidy. However, DNA aneuploidy rate in VSCCs was 38.1% , significantly higher than that in NNED and normal vulvar skins, P〈0.05. In NNED, LI was significantly higher in the aneuploidy group compared with the normal ploidy group, P=0.00. CONCLUSION： The genetic instability caused by aneuploidy may be a driving force in the early stages of vulvar carcinogenesis. DNA ploidy investigation may be of value in evaluating of the malignant potentiality of NNED.