Qureshi K N, Griffiths T R, Robinson M C, Marsh C, Roberts J T, Hall R R, Lunec J, Neal D E
Department of Urology, Royal Hallamshire Hospital, The Central Sheffield University Hospitals, Sheffield, United Kingdom.
Clin Cancer Res. 1999 Nov;5(11):3500-7.
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.
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。