Matsumoto H, Matsuyama H, Fukunaga K, Yoshihiro S, Wada T, Naito K
Department of Urology, Yamaguchi University School of Medicine, 1-1-1, Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
Br J Cancer. 2004 Sep 13;91(6):1025-31. doi: 10.1038/sj.bjc.6602073.
Invasive bladder cancers have been treated by irradiation combined with cis-platinum (CDDP) as a bladder preservative option. The aim of this study was to find a marker for predicting patient outcome as well as clinical response after chemoradiation therapy (CRT) by investigating allelic loss of apoptosis-related genes. A total of 67 transitional cell carcinomas of the bladder treated by CRT (median dose: 32.4 Gy of radiation and 232 mg of CDDP) were studied. We investigated allelic imbalances at 14 loci on chromosomes 17p13 and 1p36 including the p53 and p73 gene regions by fluorescent multiplex PCR based on DNA from paraffin-embedded tumour specimens and peripheral blood. The response to CRT was clinical response (CR) in 21 patients (31%), partial response (PR) in 31 (46%), and no change(NC) in 15 (22%). There was no statistical correlation between treatment response and clinical parameters, such as tumour grade, stage, radiation dose, or CDDP dose. The frequencies of allelic imbalance for TP53 and TP73 were 21 and 56%, respectively; neither was correlated with clinical treatment response and tumour stage or grade. There was no statistical correlation between treatment response and allelic imbalance at the other 12 loci. We found a significant correlation between cancer-specific survival and an imbalance of D1S243 (P=0.0482) or TP73 (P=0.0013) using a Log-rank test, although other loci including TP53 did not correlate with survival (P=0.4529 Multivariate analysis showed performance status (P=0.0047), recurrence (P=0.0017), and radiation doses (P=0.0468) were independent predictive factors for cancer-specific survival. However, an allelic imbalance of TP73 was the most remarkable independent predictive factor of poor patient survival (P=0.0002, risk ratio: 3382). Our results suggest that the allelic loss of the p73 gene predicts a clinical outcome of locally advanced bladder cancer when treated by CRT.
浸润性膀胱癌已采用放疗联合顺铂（CDDP）作为保留膀胱的治疗选择。本研究的目的是通过研究凋亡相关基因的等位基因缺失，寻找预测患者预后以及放化疗（CRT）后临床反应的标志物。共研究了67例接受CRT治疗的膀胱移行细胞癌（中位剂量：32.4 Gy放疗和232 mg CDDP）。我们基于石蜡包埋肿瘤标本和外周血的DNA，通过荧光多重PCR研究了17p13和1p36染色体上14个位点的等位基因失衡情况，包括p53和p73基因区域。CRT的反应为21例患者（31%）临床缓解（CR），31例（46%）部分缓解（PR），15例（22%）无变化（NC）。治疗反应与临床参数（如肿瘤分级、分期、放疗剂量或CDDP剂量）之间无统计学相关性。TP53和TP73的等位基因失衡频率分别为21%和56%；两者均与临床治疗反应、肿瘤分期或分级无关。治疗反应与其他12个位点的等位基因失衡之间无统计学相关性。使用对数秩检验，我们发现癌症特异性生存与D1S243（P = 0.0482）或TP73（P = 0.0013）的失衡之间存在显著相关性，尽管包括TP53在内的其他位点与生存无关（P = 0.4529）。多因素分析显示，体能状态（P = 0.0047）、复发（P = 0.0017）和放疗剂量（P = 0.0468）是癌症特异性生存的独立预测因素。然而，TP73的等位基因失衡是患者生存不良最显著的独立预测因素（P = 0.0002，风险比：3382）。我们的结果表明，p73基因的等位基因缺失可预测局部晚期膀胱癌接受CRT治疗后的临床结局。
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