Increased expression of cancer stem cell marker CD105, is associated with more aggressive tumor behavior in clear cell but not papillary or chromophobe renal cell carcinomas

Introduction: Renal cell carcinoma (RCC) represents 2%–3% of adult cancers and is the most lethal urological malignancy. RCC is divided into several histological subtypes. Clear cell as the most common subtype, comprises 70% of RCC cases, while papillary and chromophobe RCC are 10% to 15% and 5% of RCC cases, respectively. CD105 (endoglin) is a transmembrane glycoprotein and the receptor for transforming growth factor (TGF). Several studies have shown that endoglin contributes to the development of blood vessels and angiogenesis and is essential for tumor growth and development of metastasis. In addition, CD105 has been recently described as a cancer stem cell (CSC) marker. This study was designed to evaluate the expression and prognostic significance of the CSC marker CD105 in different histological subtypes of RCC.Materials and methods: Cytoplasmic and endothelial CD105 expressions were evaluated by immunohistochemistry in a series of RCC samples on tissue microarrays, including clear cell, type I and II papillary, and chromophobe RCCs. The association between CD105 expression, clinicopathological features as well as patients survival outcomes were determined.Results: The results exhibited that there was a statistically significant difference regarding cytoplasmic and endothelial CD105 expression among the various examined RCC subtypes (P < 0.001). In ccRCC, increased cytoplasmic and endothelial expression of CD105 were significantly associated with advanced stage, invasion to renal vein, and microvascular invasion (MVI). In addition MVI was associated with worse overall survival (OS) as well as advanced stage. Moreover, in multivariate analysis tumor stage and nuclear grade were independent prognostic factors for OS in both cytoplasmic and endothelial CD105 expression. Additionally, CD105 expression was found to be a predictor of worse OS in univariate analysis. However, in papillary and chromophobe RCC, no significant association was found between CD105 expression and clinicopathological parameters or prognosis. Conclusion: We showed that cytoplasmic and endothelial CD105 expressions were associated with more aggressive tumor behavior, tumor progression and poor OS in ccRCC patients but not in papillary and chromophobe RCC. Therefore, we consider the CSC marker CD105 as a useful prognostic molecular marker only in ccRCC, but not in other subtypes of RCC. We recommend the use of CD105 as a targeted therapy only in ccRCC cases.

Keywords:

CD105 , Renal cell carcinoma (RCC) , Cancer Stem Cells (CSCs) , Endothelial expression , Tissue microarray (TMA)