Impact of E-Cadherin and β-Catenin as Prognostic Factor in Renal Cell Carcinoma with Tumor Thrombus of the Vena Cava.

Renal cell carcinoma (RCC) forming tumor thrombus (TT) of vena cava (VC) is characterized by poor prognosis. Nevertheless, the outcome of patients after radical surgery varies. To date only limited data concerning prognostic biomarkers in this RCC subgroup are available.

Out of 159 patients with pT3b/c RCC, 95 patients without synchronous distant metastases at time of diagnosis were included in the study cohort. After immunohistochemical (IHC) evaluation of E-cadherin and β-Catenin expression, association with clinical, histopathological and survival was assessed by univariate analysis, multivariate analysis, and Kaplan-Meier-analysis. Cancer-specific survival (CSS) rates and overall survival (OS) rates were estimated using Kaplan-Meier analysis and compared using Log rank test.

We found a significant correlation between E-cadherin overexpression and initial lymph node metastasis (ρ = 0.300, p = 0.003), positive surgical margins (ρ = 0.210, p = 0.043), and the development of distant metastases (ρ = 0.258, p = 0.012). Furthermore, we observed a significant correlation of β-Catenin overexpression with higher tumor stage pT3c (ρ = 0.230, p = 0.028) and initial lymph node metastases (ρ = 0.236, p = 0.025). Survival analysis revealed a statistically significant association of both E-cadherin and β-Catenin overexpression with worse CSS (p < 0.001 and p = 0.007, respectively) and OS (p < 0.001 and p = 0.041, respectively). Multivariate analysis revealed initial lymph node metastasis as the only predictive factor for worse OS (HR 4.54, 95% CI 2.30-8.93; p < 0.001). E-Cadherin and β-Catenin expression failed to be significant in multivariable analysis for OS and CSS.

In a large series of RCC with TT of VC high IHC expression of E-cadherin and β-Catenin was associated with initial lymph node metastasis and with both worse OS and worse CSS. This might help to identify patients at risk for recurrence who might benefit from adjuvant therapy or stricter follow-up.

Urologia internationalis. 2019 Mar 07 [Epub ahead of print]

Philipp Julian Spachmann, Johannes Breyer, Charis Kalogirou, Eva-Maria Lausenmeyer, Florian Weber, Sandra Prohaska, Stefan Denzinger, Maximilian Burger, Hubert Kübler, Wolfgang Otto, Daniel Vergho

Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Regensburg, ., Department of Urology, University of Regensburg, Caritas St. Josef Medical Center, Regensburg, Germany., Department of Urology and Pediatric Urology, Julius-Maximilians University Medical Center, University of Wuerzburg, Wuerzburg, Germany., Institute of Pathology, University of Regensburg, Regensburg, Germany.