Membranous EpCAM expression is associated with higher grade and worse progression-free survival in clear cell renal cell carcinoma

Introduction: Epithelial cell adhesion/activating molecule (EpCAM) (CD326) is an interesting marker as it is one of the most frequently and most highly expressed antigens on epithelial carcinomas and plays a role in tumorigenesis and metastasis. In this study, for the first time, the membranous, cytoplasmic and nuclear expression levels of EpCAM biomarker was evaluated in three major subtypes of renal cell carcinoma (RCC). Materials and methods: Expression of EpCAM was evaluated using immunohistochemistry in 222 RCC samples on tissue microarrays including clear cell RCCs (ccRCCs), type I and II papillary (pRCC), and chromophobe RCCs (chRCC). The association between EpCAM expression and clinicopathological features as well as survival outcomes was determined.Results: Membranous EpCAM expression was observed in 110 (49.5%) patients, cytoplasmic expression in 28 (12.6%) cases and nuclear expression in 8 (3.6%). There was a statistically significant difference between EpCAM expression among the different RCC subtypes. The highly statistically significant association was observed between membranous EpCAM expression and increased nucleolar grade (P = 0.007) and histological tumor necrosis (P = 0.002). In addition, a statistically significant association was seen between cytoplasmic EpCAM expression and tumor stage (P = 0.048). We did not find any statistically significant association between nuclear EpCAM expression and any clinicopathological parameters. Moreover the results showed significant differences between progression-free survival (PFS) and the patients with high, moderate and low membranous expression of EpCAM (Log-rank test: P = 0.032). Additionally, membranous EpCAM expression was found as an independent prognostic molecular marker for PFS. In chRCC, we found a statistical significant association between only membranous EpCAM expression and tumor stage (P = 0.037), however, we did not observe a significant association between EpCAM expression and survival data. Further, no significant association was found between membranous, cytoplasmic, and nuclear EpCAM expression and important clinicopathological features and survival outcomes in type I and II pRCC.Conclusions: Our results demonstrated that increased membranous EpCAM expression is associated with more aggressiveness tumor behavior and is an independent variable favorably affecting PFS in ccRCC, therefore, EpCAM overexpression in ccRCC may be a helpful marker for prognostication and therapeutic marker for targeted therapy.

کلیدواژه ها:

EpCAM ، Renal cell carcinoma (RCC) ، Tissue microarray (TMA)