Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma:: Possible predictors for response to radiochemotherapy and successful bladder preservation
Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma:: Possible predictors for response to radiochemotherapy and successful bladder preservation
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DOI：
10.1016/s0360-3016(99)00544-1
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发表时间：
2000-03-15
影响因子：
7
通讯作者：
Sauer, R
中科院分区：
文献类型：
--
作者：
Rödel, C;Grabenbauer, GG;Sauer, R
目的：几个研究小组已经报道了通过联合治疗方案，包括经尿道切除术（TU-B）和放射化学疗法（RCT），保留膀胱的价值。随着器官保留治疗的经验越来越多，患者的选择应该优化。本研究的目的是探讨几种生物学标志物的作用，这些生物学标志物可以预测肌肉浸润性膀胱癌对RCT的反应。采用免疫组化法检测70例经TUR-B和RCT治疗的浸润性膀胱癌患者术前活检组织中的凋亡指数（AI）、Ki-67、p53和bcl-2，局部控制和保留膀胱的癌症特异性存活率。结果：高AI（>中位数= 1.6%）和高Ki-67指数（>中位数= 8.8%），而不是p53和bcl-2表达，与5年后保留膀胱的初始完全缓解（CR）和局部控制显著相关。当同时考虑AI和Ki-67表达时，与初始CR（p < 0.001）、局部控制（p = 0.0002）和保留膀胱的癌症特异性生存（p = 0.008）的相关性非常显著。在探索性多变量分析中，（最终模型），只有AI，Ki-67，和联合AI/Ki-67变量保留了5年时保留膀胱局部控制的显著性。高自发性AI和高治疗前Ki-67指数的患者应优先考虑RCT治疗，而低增殖和低凋亡水平的肿瘤不太可能对RCT有反应，（C）2000 Elsevier Science Inc.
Purpose: Several groups have reported the value of bladder preservation by a combined treatment protocol, including transurethral resection (TU-B) and radiochemotherapy (RCT), As more experience is acquired with organ-sparing treatment, patient selection should be optimized. The purpose of this study was to investigate the role of several biologic markers that may predict response to RCT in muscle-invasive bladder carcinoma.Methods and Materials: The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 70 patients treated for invasive bladder cancer by TUR-B and RCT, Expression of each marker was correlated with initial response, local control, and cancer-specific survival with preserved bladder. An exploratory multivariate analysis was also performed that included clinical and immunohistochemical variables.Results: A high AI (> median = 1.6%) and a high Ki-67 index (> median = 8.8%), but not the p53- and bcl-2 expression, were significantly related to initial complete response (CR) and local control with preserved bladder after 5 years. When the AI and Ki-67 expression were considered simultaneously, the association with initial CR (p < 0.001), local control (p = 0.0002), and cancer-specific survival with preserved bladder (p = 0.008) was highly significant. In an exploratory multivariate analysis (final model), only AI, Ki-67, and the combined AI/Ki-67 variable retained significance for local control with preserved bladder at 5 years.Conclusion: Patients with a high spontaneous AI and a high pretreatment Ki-67 index should be considered preferentially for treatment with RCT, whereas tumors with low proliferation and low levels of apoptosis are less likely to respond to RCT, (C) 2000 Elsevier Science Inc.