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

Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Expression of CYB5D2 expression is associated with epithelial-mesenchymal transition and survival rates in patients with cervical cancer

“…The study suggests that an abnormal expression of E-cadherin in CC tissues is highly correlated with the pathological features of invasion and migration of cervical malignant tumors, and it can be used for the prognosis and evaluation of CC. Results of multiple studies have indicated that downregulation of E-cadherin expression promoted lymph node metastasis ( 27 , 28 ). Although results of some studies have indicated that downregulation of E-cadherin expression is associated with lymph node metastasis, there is no correlation between them, as assessed in this study.…”

Critical Evaluation of a microRNA-Based Risk Classifier Predicting Cancer-Specific Survival in Renal Cell Carcinoma with Tumor Thrombus of the Inferior Vena Cava

“…Although constituting a high-risk setting in general, there still is substantial clinical heterogeneity within the ccRCC IVC subgroup—with reported 5-year survival rates ranging from 37% to 65% for non-metastasized patients treated with nephrectomy in combination with tumor thrombectomy [ 4 , 5 , 6 , 7 , 8 , 9 ]. Regarding this discrepancy, biomarkers are urgently needed to identify patients with a specifically high risk of cancer relapse [ 10 , 11 ]. Potentially, ccRCC IVC patients may also benefit from adjuvant systemic therapy and an intensified follow-up.…”

Evaluation of a microRNA-based Risk Classifier Predicting Cancer-Specific Survival in Renal Cell Carcinoma with Tumor Thrombus of the Inferior Vena Cava

“…While constituting a high-risk setting in general, there still is substantial clinical heterogeneity within the ccRCC IVC subgroup – with reported 5-year survival rates ranging from 37 % to 65 % for non-metastasized patients treated with nephrectomy and tumor thrombectomy [4]–[9]. Regarding this discrepancy, biomarkers are urgently needed to identify patients with a specifically high risk of cancer relapse [10], [11]. Potentially, this subgroup of ccRCC IVC patients may also benefit from adjuvant systemic therapy and additional follow-up examinations.…”