Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53
Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53
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DOI：
10.1016/s0167-8140(01)00421-2
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发表时间：
2001-11-01
影响因子：
5.7
通讯作者：
Verheij, M
中科院分区：
文献类型：
--
作者：
Ong, F;Moonen, LMF;Verheij, M
背景和目的：在最近一项针对 TUR-T 后接受根治性放疗的膀胱移行细胞癌患者的研究中，我们证明低细胞凋亡指数和 p53 阳性与局部控制不良相关。本研究的目的是评估与细胞周期和细胞凋亡调节有关的其他标志物的预后意义。 患者和方法：对 83 名接受放射治疗的膀胱浸润性移行细胞癌 (TCC) 患者的石蜡包埋治疗前活检组织进行免疫组织化学检测，检测出 Bcl-2、Bax 和 p21 阳性。此外，早期分析中确定的标志物，即：p53、细胞凋亡指数、细胞周期蛋白 D1、视网膜母细胞瘤蛋白和 Ki-67 也包含在多变量分析中。进行了逐步比例风险分析，调整了经典的预后因素（T 期、分级、多灶性和 TUR 的宏观完整性）。阳性定义为 Bcl-2、Bax 和 p21 染色阳性的肿瘤细胞>10%，p53 染色>20%。 结果：Bcl-2 阳性率为 63%，Bax 阳性率为 52%，p21 阳性率为 55%。在 PH 分析中，发现 Bcl-2 阳性与局部控制不良有关（3 年时为 36% vs. 72%；P = 0.003），以及疾病特异性生存期较短（3 年时为 74% vs. 94%；P = 0.017）。还发现了 p53 阳性不利影响的证据（局部对照：3 年时 32% vs. 69%；P = 0.037，疾病特异性生存率：3 年时 76% vs. 92%；P = 0.043）。在另一项 PH 分析中，我们发现 Bcl-2 和 p53 联合阳性的膀胱癌局部控制率较差（3 年时为 17% vs. 65%；P = 0.0017），并且疾病特异性生存率较低（60% vs. 92%；P = 0.0024）、无病生存率（7% vs. 35%，P = 0.0023）和总生存率（39% vs. 80%；P = 0.0024）较低。 P = 0.0018）。结论：这项研究为同时表达 Bcl-2 和 p53 的膀胱 TCC 接受放射治疗的患者预后不良提供了证据。发现局部控制与无病生存、疾病特异性生存和总生存之间存在这种关系。 (C) 2001 Elsevier Science Ireland Ltd. 保留所有权利。
Background and purpose: In a recent study on patients with transitional cell cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associated with poor local control. The purpose of this study was to assess the prognostic significance of additional markers implicated in regulation of cell cycle and apoptosis.Patients and Methods: Bcl-2, Bax and p21 positivity were detected immunohistochemic ally on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with radiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were included in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, multifocality and macroscopic completeness of the TUR). Positivity was defined as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53.Results: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be related to poor local control (36 vs. 72% at 3 years; P = 0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P = 0.017). Evidence for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years; P = 0.037, disease-specific survival: 76 vs. 92% at 3 years; P = 0.043). In an additional PH analysis, we found poor local control rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs. 65% at 3 years; P = 0.0017), and lower disease specific survival (60 vs. 92%; P = 0.0024), disease-free survival (7 vs. 35%, P = 0.0023) and overall survival (39 vs. 80%; P = 0.0018).Conclusion: This study provides evidence for a poor outcome in patients treated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53. This relationship was found for local control and disease-free, disease-specific and overall survival. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.