膀胱癌人乳头瘤病毒感染与Ha-ras、p53、RB基因变异及其临床意义的研究

Analysis and Clinical Implication of Ha-ras, p53 and RB Gene Mutations and Infection of Bladder Cancer with Papillomavirus

采用分子杂交、PCR-SSCP技术检测了39例膀胱癌及7例正常膀胱组织中HPV16、18感染及Ha-ras、p53、RB基因变异,并结合临床分期、病理分级等参数进行了综合分析.结果表明,膀胱癌组织中HPV16、18感染率及Ha-ras、p53、RB基因变异率分别为61.5%、36%、30.8%及15.4%;HPV阳性率与分级分期、p53基因突变与HPV感染呈明显负相关;Ha-ras、p53基因突变率与分级分期正相关,其中Ha-ras基因在复发肿瘤的突变率显著高于原发肿瘤;部分标本同时呈HPV感染与p53基因突变、Ha-ras与p53基因突变.提示高危HPV感染和Ha-ras、p53、RB基因变异及相互作用在很大程度上参与了膀胱癌的发生及演变,并与其生物学行为密切相关,有望成为判断肿瘤恶性程度、自然病程及预后的估价指标.

To clarify the clinical significance of alterations of Ha-ras, p53 and RB gene as well as infection with HPV16,18 in human bladder cancer, we examined the state of Ha-ras, p53 and RB genes, sequences of HPV16/18, and their association with clinicopathological parameters in 39 cases of bladder cancer and 7 cases of normal tissue, using nonisotopic PCR-SSCP and dot blot. The overall incidences of Ha-ras, p53 and RB gene mutation and HPV infection in tumor were 61.5% ,36% ,30.8% and 15.4% , respectively. The HPV positive rate was negatively correlated with clinical stage and pathological classification. Rather, the mutations of Ha-ras and p53 gene were positively correlated with the above clinical parameters. The incidence of Ha-ras gene mutation in recurring tumors was significantly higher than that in primary ones. A negative correlation between HPV infection and p53 mutation was also found. The results suggest that the above molecular events and their interaction play important roles in the development of bladder cancer, and that they wonld be of practical assistance in the prognosis and monitoring of bladder cancer.