Soria Francesco, Lucca Ilaria, Moschini Marco, Mathieu Romain, Rouprêt Morgan, Karakiewicz Pierre I, Briganti Alberto, Rink Michael, Gust Kilian M, Hassler Melanie R, Foerster Beat, Abufarraj Mohammad, Haitel Andrea, Klatte Tobias, Shariat Shahrokh F
Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy.
Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Lausanne University Hospital, Lausanne, Switzerland.
Urol Oncol. 2017 Jun;35(6):356-362. doi: 10.1016/j.urolonc.2017.02.009. Epub 2017 Mar 23.
Overexpression of Caveolin-1 has been associated with cancer growth, migration, and metastases in several malignancies, but only few data are available on its role in bladder cancer (BCa). The aim of this study is to validate Caveolin-1 as a prognosticator of recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in a large cohort of patients treated with radical cystectomy (RC) for BCa.
Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray from 424 patients treated with RC for UCB at a single institution. Caveolin-1 was considered overexpressed when at least 50% of the tumor cells stained positively. Univariable and multivariable Cox proportional hazards regression models were used to assess the association of Caveolin-1 expression with RFS, OS, and CSS.
Overexpression of Caveolin-1 was observed in 116 (27.4%) patients and was associated with lymph node metastasis (P = 0.003). Median follow-up for patients alive at last follow-up was 129 months (interquartile range [IQR]: 82-178). Patients with overexpression of Caveolin-1 had significant worse RFS, OS, and CSS compared to those with normal expression (log-rank test, P = 0.008, P = 0.001, and P = 0.005, respectively). At multivariable analyses that adjusted for the effects of standard clinicopathologic features, Caveolin-1 remained associated with OS (hazard ratio = 1.47, P = 0.002) and CSS (hazard ratio = 1.42, P = 0.03). Conversely, no association with RFS was found (P = 0.1). Addition of Caveolin-1 in a model for prediction of survival did not improve the accuracy of the prognostic model. Actually, C-index did not differ among models with or without Caveolin-1 (0.72 for a model predicting RFS, 0.65 for OS, and 0.71 for CSS).
Caveolin-1 is overexpressed in one-third of patients with BCa treated with RC. Overexpression of Caveolin-1 is significantly associated with OS and CSS, but not with RFS, in patients with BCa treated with RC. However, it is not clinically useful as it does not improve upon the predictive accuracy of survival achieved by pathologic variables alone.
在多种恶性肿瘤中,小窝蛋白-1(Caveolin-1)的过表达与癌症生长、迁移和转移相关,但关于其在膀胱癌(BCa)中的作用,仅有少量数据。本研究的目的是在一大群接受根治性膀胱切除术(RC)治疗的BCa患者中,验证Caveolin-1作为无复发生存期(RFS)、总生存期(OS)和癌症特异性生存期(CSS)的预后指标。
通过免疫组织化学对来自单个机构的424例接受RC治疗的上尿路膀胱癌(UCB)患者的组织芯片进行Caveolin-1表达评估。当至少50%的肿瘤细胞呈阳性染色时,认为Caveolin-1过表达。使用单变量和多变量Cox比例风险回归模型评估Caveolin-1表达与RFS、OS和CSS的相关性。
116例(27.4%)患者中观察到Caveolin-1过表达,且与淋巴结转移相关(P = 0.003)。最后一次随访时存活患者的中位随访时间为129个月(四分位间距[IQR]:82 - 178)。与表达正常的患者相比,Caveolin-1过表达的患者RFS、OS和CSS显著更差(对数秩检验,P分别为0.008、0.001和0.005)。在对标准临床病理特征的影响进行校正的多变量分析中,Caveolin-1仍与OS(风险比 = 1.47,P = 0.002)和CSS(风险比 = 1.42,P = 0.03)相关。相反,未发现与RFS相关(P = 0.1)。在生存预测模型中加入Caveolin-1并未提高预后模型的准确性。实际上,有或无Caveolin-1的模型之间C指数无差异(预测RFS的模型为0.72,OS为0.65,CSS为0.71)。
在接受RC治疗的BCa患者中,三分之一患者存在Caveolin-1过表达。在接受RC治疗的BCa患者中,Caveolin-1过表达与OS和CSS显著相关,但与RFS无关。然而,它在临床上并无用处,因为它并未提高仅由病理变量实现的生存预测准确性。