Department of Urology and Renal Transplantation, University of Foggia, Foggia, Italy.
Urol Oncol. 2010 May-Jun;28(3):285-9. doi: 10.1016/j.urolonc.2008.08.003. Epub 2008 Oct 31.
Bacillus Calmette-Guérin (BCG) immunotherapy is regarded as the current treatment of choice for stage T1 grade 3 (T1G3) bladder cancer (BC), though its efficacy is limited by high recurrence and progression rate. Identification of molecular prognosticators that might be helpful in discriminating between responders and nonresponders to BCG treatment is therefore of major clinical importance; thus we focused on the cell-cycle related retinoblastoma protein (pRB), which had been already investigated in bladder cancer. The goal of our study was specifically to address whether its expression predicts the outcomes of BCG treatment for patients with T1G3 disease.
To address this issue, paraffin-embedded specimens of 27 patients having undergone transurethral resection of T1G3 BC and intravesical instillations of BCG (induction + 1 year maintenance) were immunostained with pRB monoclonal antibody. Patients in whom the bladder muscle was not clearly visible, and healthy, as well as patients with TaG3 tumors or with concomitant carcinoma in situ were excluded. Mean follow-up was 60 months (range 15-135).
Thirteen tumors showed normal (1% to 50% labeling index) while 14 showed altered pRB expression, consisting of no expression (0% labeling index) in six and overexpression (>50% labeling index) in eight. Recurrence occurred in 10 (37%) patients and mean time to recurrence was 22.8 months (range 6-48). Recurrence rate was 57% in patients with altered and 15% in those with normal pRB expression, with a statistically significant difference in disease-free survival (P = 0.037). Progression occurred in five (18.5%) patients and mean time to progression was 24 months (range 6-48). Progression rate was 36% in patients with altered and 0% in patients with normal pRB expression, with a statistically significant difference in progression-free survival (P = 0.018).
In this homogeneous population of T1G3 bladder tumors, altered pRB expression predicted recurrence and progression after BCG treatment. These findings outline the potential role of pRB immunostaining in predicting T1G3 BC response to BCG immunotherapy.
卡介苗（BCG）免疫疗法被认为是治疗 T1 级 3 期（T1G3）膀胱癌（BC）的当前首选治疗方法，但其疗效受到高复发和高进展率的限制。因此，鉴定可能有助于区分对 BCG 治疗有反应和无反应的患者的分子预后标志物具有重要的临床意义；因此，我们专注于细胞周期相关的视网膜母细胞瘤蛋白（pRB），该蛋白已在膀胱癌中进行了研究。我们研究的目的是专门探讨其表达是否可以预测 T1G3 疾病患者接受 BCG 治疗的结果。
为了解决这个问题，对 27 名接受经尿道 T1G3BC 切除术和膀胱内 BCG 灌注（诱导+ 1 年维持）的患者的石蜡包埋标本进行了 pRB 单克隆抗体免疫染色。排除膀胱肌肉不可见的患者、健康患者、TaG3 肿瘤患者和同时患有原位癌的患者。平均随访时间为 60 个月（范围 15-135）。
13 个肿瘤表现为正常（1%至 50%标记指数），而 14 个肿瘤表现为 pRB 表达改变，包括 6 个肿瘤无表达（0%标记指数）和 8 个肿瘤过度表达（>50%标记指数）。10 名患者（37%）出现复发，平均复发时间为 22.8 个月（范围 6-48）。pRB 表达改变的患者复发率为 57%，正常表达的患者复发率为 15%，疾病无进展生存率有统计学差异（P=0.037）。5 名患者（18.5%）出现进展，平均进展时间为 24 个月（范围 6-48）。pRB 表达改变的患者进展率为 36%，正常表达的患者进展率为 0%，无进展生存率有统计学差异（P=0.018）。
在这个同质的 T1G3 膀胱癌患者群体中，pRB 表达改变预测了 BCG 治疗后的复发和进展。这些发现概述了 pRB 免疫染色在预测 T1G3BC 对 BCG 免疫治疗反应中的潜在作用。
