膀胱移行细胞癌细胞DNA含量、rasp21和p53蛋白表达的综合定量研究

Quantitative studies of DNA content, ras and p53 oncoprotein expression in urinary bladder transitional carcinomas

目的：探讨细胞ＤＮＡ含量、抑癌基因ｐ５３和癌基因ｒａｓ表达在膀胱移行细胞癌发生发展中的综合作用及其与临床病理特征的关系。方法：以免疫流式细胞光度术与病理形态学相结合的方法对５６例膀胱移行细胞癌细胞ＤＮＡ含量、ｒａｓｐ２１和ｐ５３蛋白表达进行了定量研究。结果：研究发现，本组膀胱移行细胞癌不管从Ｓ％、ＰＩ还是ＤＩ均明显高于正常膀胱粘膜上皮，其平均ＤＩ已处于ＤＮＡ异倍体范围。癌基因ｒａｓｐ２１的阳性表达及抑癌基因ｐ５３的异常表达率分别为６２．５％和７６．７％。随膀胱移行细胞癌分化程度的降低，肿瘤细胞增殖活性（Ｓ％、ＰＩ）和ＤＮＡ含量及ＤＮＡ异倍体出现率均增高，Ⅲ级组上述参数明显高于Ⅰ、Ⅱ级组和对照组（Ｐ分别＜０．０１，０．０２和０．０１）。ｒａｓｐ２１和ｐ５３表达的阳性率随分化程度的降低而明显增高，Ⅲ级病例ｐ５３的阳性表达率达１００％，ｒａｓｐ２１的阳性表达率亦达８０％，且其表达强度亦高于Ⅰ／Ⅱ级组。此外，分化越低，ｒａｓｐ２１＋／ｐ５３＋和ｒａｓｐ２１＋／ｐ５３＋／ＤＮＡ异倍体病例亦越多（Ｐ＜０．０５）。结论：膀胱移行细胞癌的发生发展是多种因素协同作用的结果，从遗传物质ＤＮＡ到癌基因ｒａｓ家族和抑癌基因ｐ５３在?

Purpose: To explore the possible role of cellular DNA, tumor supperssor gene p53 as well as oncogene ras expression on the carcinogenesis and development of bladder transitional carcinoma and their relationship with clinical pathological features. Method: Nuclear DNA contents, oncogene ras and tumor suppressor gene p53 expression at protein level were studied on 56 cases of bladder transitional carcinoma with flow cytometric (FCM) and pathological methods. Results: The results showed that S fraction, proliferation index (PI) and DNA contents (as presented by DNA Index, DI) of the bladder carcinomas were all significantly higher than those of normal transitional epithelia and the mean DI of the former was in DNA aneuploid range. Positive rate for ras p21 and p53 oncoprotein expression was 62.5% and 76.7%, respectively. The proliferation activity (S%, PI) and nuclear DNA content as well as frequency of DNA aneuploid increased with the differentiation of the bladder cancer decreased. All the parameters mentioned above for grade Ⅲ carcinoma were significantly higher than those for grade Ⅰ and Ⅱ as well as normal control (P<0.01,P<0.02,P<0.01, respectively). Ras p21 and p53 positive expression rate in grade Ⅲ carcinoma was 100% and 80%, respectively. Ras p21+/p53+and ras p21+/p53+/DNA aneuploid cases in low differentiated (grade Ⅲ) carcinoma were more frequently seen than in well and moderate differentiated cases (80%, 34.7%, 60.8% for ras p21 and p53 coexpression and 50%, 13%, 21.7% for ras p21 and p53 coexpression and DNA aneupliod, P<0.05). Conclusion: Thus the results in this study suggest that oncogene ras family, tumor suppressor gene p53 as well as DNA participated in the carcinogenesis and development of bladder transitional carcinoma.