Kuczyk M A, Bokemeyer C, Serth J, Hervatin C, Oelke M, Höfner K, Tan H K, Jonas U
Department of Urology, Hannover Medical School, Germany.
Eur J Cancer. 1995 Dec;31A(13-14):2243-7. doi: 10.1016/0959-8049(95)00443-2.
Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T2-T4) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (> or = 80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.
免疫组化检测发现TP53基因蛋白过表达似乎可识别出那些有发生肌肉浸润性或转移性疾病风险的浅表性膀胱癌患者。然而,p53过表达在晚期或转移性膀胱癌患者中的作用尚未完全明确。在本研究中,对44例接受根治性膀胱切除术的晚期膀胱肿瘤(T2 - T4期)患者的44份标本进行了研究,以探讨不同的生物学和临床特征作为可能的预后因素:性别、年龄、肿瘤浸润深度、T分期、组织学分级、淋巴结状态、辅助全身化疗(MVAC)的应用、增殖活性(用单克隆抗体(PC10)对增殖细胞核抗原(PCNA)进行染色)以及p53癌蛋白的过表达(单克隆抗体pAb 1801)。中位随访22个月后,23例肿瘤细胞p53染色阳性率超过40%的患者(B组)中有16例(70%)死于肿瘤进展,而21例肿瘤细胞p53染色阳性率低于40%的患者中有7例(33%)死于肿瘤进展。在单因素分析中,p53过表达(P = 0.008)、PCNA染色(≥80%细胞阳性)(P = 0.01)和肿瘤分期(P = 0.01)是生存的显著预后因素,其中在多因素分析中,p53过表达(P = 0.023)以及T分期(P = 0.012)仍然是独立的显著预测因素。需要进行前瞻性研究以证实p53过表达在晚期膀胱癌患者中的独立预后潜力。更精确的预后因素的可用性应有助于就更积极的治疗选择(如辅助或新辅助化疗)对预后明确的患者亚组的价值做出决策。