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TP53蛋白积累预示着对基于顺铂的全身化疗耐药的肌层浸润性膀胱癌患者的生存率提高。

TP53 accumulation predicts improved survival in patients resistant to systemic cisplatin-based chemotherapy for muscle-invasive bladder cancer.

作者信息

Qureshi K N, Griffiths T R, Robinson M C, Marsh C, Roberts J T, Hall R R, Lunec J, Neal D E

机构信息

Department of Urology, Royal Hallamshire Hospital, The Central Sheffield University Hospitals, Sheffield, United Kingdom.

出版信息

Clin Cancer Res. 1999 Nov;5(11):3500-7.

PMID:10589764
Abstract

To examine retrospectively the prognostic significance of TP53 immunoreactivity for both tumor response and patient survival in 83 patients with nonmetastatic muscle-invasive bladder cancer treated with a single transurethral resection (TUR) of tumor and combined cisplatin-based systemic chemotherapy followed by repeat TUR, paraffin-embedded sections of a bladder tumor obtained at TUR before chemotherapy (1 T2, 52 T3, and 30 T4) were immunostained for TP53 using monoclonal PAb1801 and DO-7 antibodies. For the entire cohort, TP53 immunopositivity (PAb1801 or DO-7) did not predict complete response (CR), complete or partial response (PR), progressive disease, or time to death from bladder cancer. There was a highly significant correlation between PAb1801 and DO-7 nuclear immunoreactivity (r = 0.8242; P<0.0001). In 76 patients in which complete clinical data were available, tumor stage (T2/T3; P = 0.0499), CR and PR (P = 0.0016) and CR (P<0.0001) were associated with patient survival. In a multivariate model, CR (P<0.0001) was the only independent predictor of improved survival. In complete responders, neither TP53 immunostaining nor clinicopathological factors stratified patients into prognostic groups. However, in the subset of patients (n = 38) who were chemoresistant (PR or progressive disease), improved survival was associated with > or =20% TP53 immunoreactivity (PAb1801; P = 0.0191) and tumor stage (T2/T3; P = 0.0358). TP53 immunopositivity (PAb1801 or DO-7) did not predict overall survival or response to systemic chemotherapy in patients with nonmetastatic but predominantly clinical stage > or =T3 bladder cancer, but it had prognostic significance within the chemoresistant subgroup.

摘要

回顾性研究83例非转移性肌层浸润性膀胱癌患者经单次经尿道肿瘤切除术(TUR)及顺铂为主的全身化疗后重复TUR治疗,TP53免疫反应性对肿瘤反应和患者生存的预后意义。对化疗前TUR获取的膀胱肿瘤石蜡包埋切片(1例T2、52例T3和30例T4),使用单克隆PAb1801和DO-7抗体对TP53进行免疫染色。对于整个队列,TP53免疫阳性(PAb1801或DO-7)不能预测完全缓解(CR)、完全或部分缓解(PR)、疾病进展或膀胱癌死亡时间。PAb1801和DO-7核免疫反应性之间存在高度显著相关性(r = 0.8242;P<0.0001)。在76例有完整临床数据的患者中,肿瘤分期(T2/T3;P = 0.0499)、CR和PR(P = 0.0016)以及CR(P<0.0001)与患者生存相关。在多变量模型中,CR(P<0.0001)是生存改善的唯一独立预测因素。在完全缓解者中,TP53免疫染色和临床病理因素均未将患者分层为预后组。然而,在化疗耐药(PR或疾病进展)的患者亚组(n = 38)中,生存改善与TP53免疫反应性≥20%(PAb1801;P = 0.0191)和肿瘤分期(T2/T3;P = 0.0358)相关。TP53免疫阳性(PAb1801或DO-7)不能预测非转移性但主要临床分期≥T3膀胱癌患者的总生存或对全身化疗的反应,但在化疗耐药亚组中具有预后意义。

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