Serth J, Kuczyk M A, Bokemeyer C, Hervatin C, Nafe R, Tan H K, Jonas U
Department of Urology, Hannover University Medical School, Germany.
Br J Cancer. 1995 Jan;71(1):201-5. doi: 10.1038/bjc.1995.41.
Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those patients who develop muscle-invasive tumours or metastatic disease at recurrence do poorly clinically. In the current study 69 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, performance of instillation therapy and immunohistochemical determination of mutational inactivation of p53 tumour-suppressor gene (monoclonal antibody PAb 1801) as well as immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). After a median follow-up of 45.8 months, 12 of 14 patients (85.7%) with more than 20% of cells positive for p53 had disease progression with muscle-invasive growth compared with only one of 55 patients (1.8%) negative for p53 (P < 0.01, chi 2 test). During univariate analysis histological grade (G1 vs G2) (P = 0.0373), positivity for PCNA (> 60% of cells) (P = 0.0033) and positivity for p53 (P < 0.001) were significant prognostic factors for disease progression (log-rank test), while during multivariate analysis only positivity for p53 was a significant predictor for relapse of bladder cancer (P = 0.0029) (multivariate Cox regression analysis). The immunohistochemical detection of mutations of the p53 gene has been demonstrated to be a reliable, easily performed and thereby widely available technique for the investigation of fresh-frozen or paraffin-embedded tumour specimens. The results demonstrate the important role of the p53 tumour-suppressor gene protein in the development and for the progression of bladder cancer. If the high prognostic value of p53 mutations in superficial bladder cancer is confirmed in larger prospective trials, more aggressive therapeutic strategies could be discussed for patients with p53 mutations in their tumour specimens.
尽管浅表性膀胱癌（Ta、T1）患者的总体预后通常较好，但那些复发时出现肌肉浸润性肿瘤或转移性疾病的患者临床预后较差。在本研究中，对69例因膀胱浅表性移行细胞癌接受经尿道完全切除术的患者进行了调查，以研究不同的临床和生物学特征作为可能的预后因素：年龄、性别、灌注治疗情况、通过p53肿瘤抑制基因突变失活的免疫组化测定（单克隆抗体PAb 1801）以及通过PCNA（增殖细胞核抗原）染色（单克隆抗体PC 10）进行增殖率的免疫组化测定。中位随访45.8个月后，14例p53阳性细胞超过20%的患者中有12例（85.7%）出现疾病进展并伴有肌肉浸润性生长。相比之下，55例p53阴性患者中只有1例（1.8%）出现这种情况（P<0.01，卡方检验）。在单因素分析中，组织学分级（G1对G2）（P = 0.0373）、PCNA阳性（>细胞数的60%）（P = 0.0033）和p53阳性（P<0.001）是疾病进展的显著预后因素（对数秩检验），而在多因素分析中，只有p53阳性是膀胱癌复发的显著预测因素（P = 0.0029）（多因素Cox回归分析）。p53基因突变的免疫组化检测已被证明是一种可靠、易于操作且广泛可用的技术，可用于新鲜冷冻或石蜡包埋肿瘤标本的研究。结果表明p53肿瘤抑制基因蛋白在膀胱癌的发生和进展中具有重要作用。如果在更大规模的前瞻性试验中证实p53突变在浅表性膀胱癌中的高预后价值，那么对于肿瘤标本中存在p53突变的患者，可以讨论更积极的治疗策略。
