膀胱癌中p53突变及Bcl-2、PCNA表达与细胞的增殖和凋亡

目的　探讨膀胱癌中p5 3突变和Bcl 2、增殖细胞核抗原 (PCNA)表达与细胞增殖、凋亡和临床病理学参数之间的关系。方法　SABC免疫组化检测 6 2例膀胱癌标本Bcl 2、p5 3和PCNA的表达。计算肿瘤细胞中PCNA阳性细胞百分比即增殖指数 (PI)。TUNEL法检测细胞凋亡 ,计算肿瘤细胞中凋亡细胞的百分比即凋亡指数 (AI)。结果　 6 2例膀胱癌中 ,5 0例 (80 6 % )发生 p5 3突变 ,其中G3 级的突变率为 91 3% ,较G1级 (72 7% )和G2 级(78 5 % )更多见 ,但差异无显著性意义 (P >0 0 5 ) ;T2 期 p5 3突变率 (95 7% )较Ta 1期 (71 8% )高 (P <0 0 1)。14例 (2 2 5 % )发现有Bcl 2表达 ,Bcl 2表达阳性率在G3 级中明显高于G1和G2 级 (P <0 0 5 ) ,但与分期无相关性(P >0 0 5 )。Bcl 2表达与p5 3突变无关。PI为 17 3%～ 4 1 8% (平均为 2 2 4 % ) ,AI为 1 9%～ 3 5 % (平均为2 9% ) ,PI与肿瘤分级、分期相关 ,AI与肿瘤的分级明显相关。结论　p5 3突变与浸润性行为呈正相关。在膀胱癌中 p5 3和PCNA过表达可提示预后。随着肿瘤的进展 ,肿瘤细胞过度增殖可能伴有频繁的凋亡 ,但增殖指数的增加明显强于凋亡指数的增加。

Relationship of Cell Proliferation and Apoptosis with p53 Mutation, PCNA and Bcl-2 Expression in Bladder Transitional Cell Carcinoma

Objective To investigate the relationship between the frequency of p53 mutation, Bcl-2 and PCNA expression with cell proliferation, apoptosis and clinicopathologic parameters in the patients with bladder cancer. Methods Paraffin-embedded sections from primary transitional cell carcinomas (TCC) in bladder were investigated immunohistochemically for p53, Bcl-2 and PCNA. The proliferation index (PI) was expressed as a percentage of the PCNA-positive cells in the tumor cells. Apoptosis was detected by terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and the apoptotic index (AI) was expressed as a percentage of the TUNEL-positive cells in the tumor cells. Results p53 mutation was identified in 50 patients (80.6 %). The mutation was most common in grade 3 tumors (91.3 %) as compared to grade 2 (78.5 %) and grade 1 (72.7 %) tumors, but the difference was not statistically significant (P>0.05). Stage T_2 tumors had higher incidence of p53 mutation (95.7 %) as compared to T tumors (71.8 %, P<0.01). Only 14 tumors (22.5 %) expressed Bcl-2; The grade 3 tumors had significantly higher incidence of Bcl-2 expression (P<0.05), and there was no correlation between Bcl-2 and stage. There was no interrelation between p53 mutation and Bcl-2 expression (P>0.05). The PI ranged from 17.3 % to 41.8 % (median 22.4 %) and the AI from 1.9 % to 3.5 % (median 2.9 %) in bladder cancer. Statistical analysis revealed close associations between PI, AI and tumor grade and stage of bladder cancer. Conclusion p53 mutation was positively correlated with invasive disease. p53 and PCNA over-expression may offer valuable additional prognostic information in bladder tumors. With the progression of the tumor grade, cell proliferation may be accompanied by frequent apoptosis in bladder cancer, but the increment of PI was much larger than that of AI.