Expression of bcl-2 and bcl-X in bladder cancer
Expression of bcl-2 and bcl-X in bladder cancer
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DOI：
10.1016/s0022-5347(01)63614-0
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发表时间：
1998-04-01
影响因子：
6.6
通讯作者：
Stadler, WM
中科院分区：
文献类型：
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作者：
Kirsh, EJ;Baunoch, DA;Stadler, WM
目的：膀胱移行细胞癌（TCC）中TP 53和RBI基因突变与分级、分期、复发和生存相关，并可能与肿瘤细胞凋亡潜能相关。bcl-2和bcl-X抗凋亡基因的过表达与其他系统的不良预后和化疗耐药性相关。尚未在TCC中进行类似研究。因此，我们试图确定bcl-2和bcl-X在TCC的表达，并与这些阶段，生存和异常pRb或p53 expression.Materials和方法：42 TCC样本（19 Ta和23个局部晚期肿瘤）和正常尿路上皮对照进行了检查。p53、pRb、bcl-2和bcl-X的免疫组织化学在自动系统上使用间接链霉亲和素生物素/辣根过氧化物酶染色进行。对膀胱癌细胞系进行Western免疫印迹分析以进一步表征bcl-X表达。回顾性确定无复发和疾病特异性生存率。Kaplan-Meier生存曲线进行比较，使用对数秩检验，和相关性的异常染色与阶段和p53或pRb状态确定使用Fisher的精确test.Results：Bcl-2表达在不到1%的正常尿路上皮细胞，但中度表达的bcl-x被发现在所有正常尿路上皮样本。只有7.0%的TCC（1/19 Ta和2/23局部晚期肿瘤）表现出bcl-2过表达。45.2%的TCC（8/19例Ta和11/23例局部晚期肿瘤）中观察到Bcl-X过表达。Western印迹分析还显示，长（29 kDa）抗凋亡形式和短（19 kDa）促凋亡形式在膀胱癌细胞系和正常人尿路上皮细胞中过表达。Bcl-X过度表达与正常p53表达弱相关（p = 0.06）。bcl-2和bcl-X的过度表达与p53、pRb异常及肿瘤分期无关。有异常bcl-X染色的患者无复发或总生存率无差异。结论：Bcl-2过表达是罕见的TCC。Bcl-X过度表达是常见的，可能反映了其在正常尿路上皮中的表达模式，但与分期或异常p53或pRb染色无关。在这项小型研究的能力范围内，bcl-X过表达与复发或生存无关。
Purpose: TP53 and RBI gene mutations in bladder transitional cell carcinoma (TCC) are correlated with grade, stage, recurrence, and survival and may correlate with tumor cell apoptotic potential. Overexpression of the bcl-2 and bcl-X anti-apoptotic genes has been correlated with poor prognosis and chemotherapy resistance in other systems. Similar studies have not been performed in TCC. We thus sought to determine expression of bcl-2 and bcl-X in TCC and correlate these with stage, survival and abnormal pRb or p53 expression.Materials and Methods: Forty-two TCC samples (19 Ta and 23 locally advanced tumors) and normal urothelial controls were examined. Immunohistochemistry for p53, pRb, bcl-2 and bcl-X was performed on an automated system using indirect streptavidin biotin/horseradish peroxidase staining. Western immunoblot analysis was performed on bladder cancer cell lines to further characterize bcl-X expression. Recurrence-free and disease-specific survival were retrospectively determined. Kaplan-Meier survival curves were compared using the log rank test, and correlation of abnormal staining with stage and p53 or pRb status was determined using Fisher's exact test.Results: Bcl-2 was expressed in less than 1% of normal urothelial cells, but moderate expression of bcl-x was found in all normal urothelial samples. Only 7.0% of TCC samples (1/19 Ta and 2/23 locally advanced tumors) demonstrated bcl-2 overexpression. Bcl-X overexpression was observed in 45.2% of TCC (8/19 Ta and 11/23 locally advanced tumors). Western blot analysis also revealed that both the long (29 kDa) anti-apoptotic form and short (19 kDa) pro-apoptotic form were overexpressed in bladder cancer cell lines and normal human urothelial cells. Bcl-X overexpression was weakly correlated with normal p53 expression (p = 0.06). There were no correlations of bcl-2 and bcl-X overexpression with abnormal p53, pRb, or tumor stage. There were no differences in recurrence-free or overall survival in patients with abnormal bcl-X staining.Conclusions: Bcl-2 overexpression is rare in TCC. Bcl-X overexpression is common, likely reflecting its expression pattern in normal urothelium, but is not correlated with stage or abnormal p53 or pRb staining. Within the power Limitations of this small study, bcl-X overexpression is not correlated with recurrence or survival.