Sarkis A S, Dalbagni G, Cordon-Cardo C, Zhang Z F, Sheinfeld J, Fair W R, Herr H W, Reuter V E
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021.
J Natl Cancer Inst. 1993 Jan 6;85(1):53-9. doi: 10.1093/jnci/85.1.53.
Approximately one third of the patients with superficially infiltrative transitional cell (T1-TNM pathological staging system) bladder carcinoma who are treated with transurethral resection alone have disease progression. Despite precise pathologic staging and grading, clinical outcome in these patients is not predictable. Recent reports reveal that mutations of the p53 tumor suppressor gene (also known as TP53) occur commonly in bladder cancers.
The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein product(s) of the mutated p53 tumor suppressor gene are associated with tumor progression in patients with T1 bladder cancer.
We examined deparaffinized tumor tissue specimens from transurethral resection in 43 patients with T1 bladder cancer who had not received adjuvant therapy. Nuclear overexpression of p53 protein was detected by immunohistochemical analysis using the mouse monoclonal antibody PAb1801, which stains both wild-type and mutant p53 proteins. The data were then correlated with the following conventional prognostic variables: age, sex, histologic presence of associated carcinoma in situ, and vascular invasion of tumor. Disease progression rates per 100 person-years were calculated.
Median follow-up was 119 months. None of the urothelial and stromal cells from normal bladder specimens showed nuclear overexpression of p53 protein, but patients with T1 bladder tumors could be stratified into two groups with different patterns of staining for p53 protein. Eighteen patients (42%) had no more than 20% tumor cells with positive nuclear staining (group A), while the remaining 25 patients (58%) had 20% or more tumor cells with nuclear immunoreactivity (group B). Patients in group B had a significantly lower progression-free interval (P < .001). Disease progression rates were 20.5% per year for group B and 2.5% for group A.
These results suggest that T1 bladder cancers exhibiting nuclear overexpression of p53 protein have a higher probability of disease progression. This study also suggests that p53 overexpression is an important prognostic factor in these patients and may be useful in selecting appropriate therapy.
Large prospective studies are needed to confirm these results and to evaluate nuclear overexpression of p53 protein as a prognostic marker in bladder cancer.
在仅接受经尿道切除术治疗的浅表浸润性移行细胞癌（T1 - TNM病理分期系统）患者中，约三分之一会出现疾病进展。尽管进行了精确的病理分期和分级，但这些患者的临床结局仍无法预测。最近的报告显示，p53肿瘤抑制基因（也称为TP53）的突变在膀胱癌中普遍存在。
本研究的目的是调查以下假设，即突变的p53肿瘤抑制基因的蛋白质产物表达模式改变与T1期膀胱癌患者的肿瘤进展相关。
我们检查了43例未接受辅助治疗的T1期膀胱癌患者经尿道切除术后的石蜡包埋肿瘤组织标本。使用小鼠单克隆抗体PAb1801通过免疫组织化学分析检测p53蛋白的核过表达，该抗体可对野生型和突变型p53蛋白进行染色。然后将数据与以下传统预后变量相关联：年龄、性别、原位癌的组织学存在情况以及肿瘤的血管侵犯情况。计算每100人年的疾病进展率。
中位随访时间为119个月。正常膀胱标本的尿路上皮细胞和基质细胞均未显示p53蛋白的核过表达，但T1期膀胱肿瘤患者可分为两组，其p53蛋白染色模式不同。18例患者（42%）的肿瘤细胞核染色阳性细胞不超过20%（A组），其余25例患者（58%）的肿瘤细胞核免疫反应阳性细胞达到20%或更多（B组）。B组患者的无进展生存期明显更短（P <.001）。B组的疾病进展率为每年20.5%，A组为2.5%。
这些结果表明，表现出p53蛋白核过表达的T1期膀胱癌疾病进展的可能性更高。本研究还表明，p53过表达是这些患者的重要预后因素，可能有助于选择合适的治疗方法。
需要进行大型前瞻性研究来证实这些结果，并评估p53蛋白核过表达作为膀胱癌预后标志物的价值。
