Cordon-Cardo C, Wartinger D, Petrylak D, Dalbagni G, Fair W R, Fuks Z, Reuter V E
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021.
J Natl Cancer Inst. 1992 Aug 19;84(16):1251-6. doi: 10.1093/jnci/84.16.1251.
It has been reported that 50%-70% of patients with bladder cancer experience recurrence after initial successful treatment and about 10%-20% of these patients die of the disease. Despite precise pathologic staging and grading, we are unable to predict clinical outcome in all patients. The retinoblastoma-susceptibility (RB) gene, a prototype of tumor suppressor genes, has recently been associated with development and/or progression of bladder cancer, as well as sarcoma and small-cell lung cancer. In transitional cell carcinomas of the bladder, we have observed altered expression of the Rb gene product--a nuclear phosphoprotein thought to function as a cell cycle regulator.
The aim of this study was to investigate the hypothesis that altered patterns of Rb expression correlate with prognosis in bladder cancer.
Expression of the RB gene was evaluated in specimens from 48 primary bladder tumors obtained by cystectomy or transurethral resection. Rb protein expression was correlated with disease outcome in these patients. Rb expression was examined by immunohistochemistry, using the mouse monoclonal antibody Rb-PMG3-245 on frozen tissue sections. Computerized image analysis was used to quantify the level of Rb protein in individual tumor cells.
The overall 5-year disease-free survival was 66%, with a median follow-up of 42 months. Normal levels of Rb protein expression were found in 34 patients (Rb-positive group). A spectrum of altered patterns of expression from undetectable levels to heterogeneous expression, however, was observed in 14 patients (altered Rb group). Of the 38 patients with muscle-invasive tumors, 13 were categorized as having altered expression of Rb protein. Only one of 10 patients with superficial carcinomas had altered expression of Rb protein. The 5-year survival was significantly decreased in patients with altered Rb protein compared with the survival in patients with positive Rb expression (P less than .001).
The results suggest that tumors exhibiting decreased expression of the RB gene-coded product (Rb protein) had a more aggressive biological behavior than those that expressed the Rb protein in the majority of their tumor cells.
This study demonstrates that altered patterns of Rb protein expression may be an important prognostic variable in patients presenting with invasive bladder cancer.
据报道，50%-70%的膀胱癌患者在初始成功治疗后会复发，其中约10%-20%的患者死于该疾病。尽管有精确的病理分期和分级，但我们仍无法预测所有患者的临床结局。视网膜母细胞瘤易感（RB）基因作为肿瘤抑制基因的原型，最近已被发现与膀胱癌、肉瘤和小细胞肺癌的发生和/或进展有关。在膀胱移行细胞癌中，我们观察到Rb基因产物（一种被认为作为细胞周期调节因子发挥作用的核磷蛋白）的表达发生了改变。
本研究的目的是调查Rb表达模式改变与膀胱癌预后相关这一假说。
通过膀胱切除术或经尿道切除术获取48例原发性膀胱肿瘤标本，评估RB基因的表达情况。将Rb蛋白表达与这些患者的疾病结局相关联。使用小鼠单克隆抗体Rb-PMG3-245对冰冻组织切片进行免疫组织化学检查以检测Rb表达。采用计算机图像分析对单个肿瘤细胞中Rb蛋白的水平进行定量。
总体5年无病生存率为66%，中位随访时间为42个月。34例患者（Rb阳性组）的Rb蛋白表达水平正常。然而，在14例患者（Rb表达改变组）中观察到了从不可检测水平到异质性表达的一系列表达模式改变。在38例肌肉浸润性肿瘤患者中，13例被归类为Rb蛋白表达改变。10例浅表性癌患者中只有1例Rb蛋白表达改变。与Rb表达阳性的患者相比，Rb蛋白表达改变的患者5年生存率显著降低（P<0.001）。
结果表明，与那些在大多数肿瘤细胞中表达Rb蛋白的肿瘤相比，表现出RB基因编码产物（Rb蛋白）表达降低的肿瘤具有更具侵袭性的生物学行为。
本研究表明，Rb蛋白表达模式的改变可能是浸润性膀胱癌患者的一个重要预后变量。
