膀胱移行细胞癌中p53突变、bcl-2和PCNA表达的临床意义

目的　　探讨膀胱癌中bcl-2、p53、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 免疫组化分折62例(T1GI —G339 例,T2-T4aG3　NOM023例)甲醛固定和石蜡包埋的膀胱癌标本bcl-2、p53 和PCNA蛋白的免疫反应性。平均随访37个月,24例复发。增殖指数(PI)表示肿瘤细胞中PCNA阳性细胞百分比。TUNEL法检测细胞凋亡,凋亡指数(AI)表示肿瘤细胞中凋亡细胞的百分比。结果　　62例膀胱癌中,50例(80.0%)发生p53突变,与G1(72.7%)和G2(78.5%)相比较G3(91.3%)更多见(P<0.05);pT2期(95.7%)p53突变率较pTa-1期(74.3%)高(P<0.叭)。14例(22.5%)发现有bel-2表达,bcl-2表达阳性率G3明显高于G1和G2(P<0.05),与分期无关(P>0.05)。Bcl-2表达与p53突变无关。在膀胱癌中,PI 为17.2%～41.8%(平均为22.4%),AI为1.9%-3.5%(平均为2.9%)。统计分析显示PI与肿瘤分级、分期关系密切,AI与肿瘤的分级有明显关系。结论　　结果表明,p53突变与浸润性行为呈正相关。在膀胱癌中p53和PCNA过表达可能能提供有价值的预后信息。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。

Clinical Significance of p53, Proliferating Cell Nuclear Antigen and bcl-2 Expression in Bladder Transitional Cell Carcinoma

Objective: To correlate the frequency of p53 mutations, bcl-2 expression and the proliferation status (proliferating cell nuclear antigen, PCNA) in patients with bladder cancer with cell proliferation, apoptosis and their clinico-pathologic ?ndings. Methods: Para?n-embedded sections from 39 super?cial (T1G1-G3) and 23 invasive (T2-T4a G3 N0M0) primary transitional cell carcinomas (TCC) in the bladder were investigated immunohistochemically for p53, bcl-2 and PCNA. The median follow-up was 37 months; 24 had recurrences. 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 tumor cells. Results: P53 mutation was identi?ed in 50 patients (80.6%). The mutation was most common in tumors of grade 3 (91.3%) as compared to grade 2 (78.5%) and grade 1 (72.7%, P<0.05). Stage pT2 tumors had a higher frequency of p53 mutation (95.7%) as compared to pTa-1 tumors (74.3%, P<0.01). Only 14 tumors (22.5%) expressed bcl-2; grade 3 tumors expressed bcl-2 signi?cantly more frequently (P<0.05); there was no correlation between bcl-2 and tumor stage. There was no interrelation between p53 mutation and bcl-2 expression (P>0.05). The PI ranged from 17.2% to 41.8% (median 22.4%) and the AI from 1.9% to 3.5% (median 2.9%) in bladder cancer. Statistical analyses revealed a close associations between PI, AI and tumor grade and stage of bladder cancer. Conclusion: P53 mutation correlates with invasion. P53 and PCNA overexpression may o?er 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 PI increased much more than the AI.