Epithelial cell adhesion molecule is an independent prognostic marker in clear cell renal carcinoma

Abstract

Epithelial cell adhesion molecule (EPCAM) has recently attained a renewed interest as a candidate protein in diagnosis, prognostication and therapy of various tumor entities. The molecular epidemiology and prognostic relevance of EPCAM in renal cell carcinoma (RCC) and amongst the histological subtypes of RCC are unclear. We analyzed the prevalence and prognostic significance of EPCAM in a tumor tissue microarray composed of 1,088 independent RCCs samples by immunohistochemistry (IHC). We found significant variations of EPCAM IHC staining intensities in between the RCC subtypes: in papillary and chromophobe RCC, the majority of tumors (89-93%) showed an at least weak EPCAM protein expression. In the largest subgroup, the clear cell (cc)RCC (n 5 767), a negative EPCAM IHC was found in 1/3 of the patients and was associated with high-grade disease and nodal metastases. Kaplan-Meier analyses demonstrated a significant association between positive EPCAM IHC and prolonged overall survival, even in a subset of low-risk ccRCC. In multivariable analyses, EPCAM represented an independent risk factor of survival throughout all subgroups. For localized, low-grade ccRCC, information of EPCAM IHC raised predictive accuracy of a multivariate model by~5%, compared to T-stage and grade alone. Our findings indicate that EPCAM is an independent prognostic molecular marker in ccRCC and, especially in localized ccRCC, might be able to provide auxiliary information for a better prognostication.Today, the majority of diagnosed and treated renal cell carcinomas (RCC) represent early-stage tumors, assuming a high cure probability after localized therapy. Counterintuitively, the cancer-specific mortality rates have been rising over the last decades displaying RCC's rather unpredictable nature of disease.

Expression of EpCAMMFand EpCAMMTvariants in human carcinomas

“…Our group could show that EpCAM can act both as tumour suppressor and tumour promotor28 29 in breast cancer cell lines and the dual role of EpCAM was confirmed by a recent study in breast cancer patients 30. Only recently, Eichelberg et al 31 reported a positive EpCAM status to be significantly associated with a prolonged overall survival in renal cell carcinoma. Moreover, the prognostic value of cytoplasmic accumulation of EpCAM was demonstrated in patients with node positive breast cancer 17.…”

Microarrays and Renal Cell Cancer Biomarkers

“…Although strong expression was seen in only 10 % of 318 ccRCC, EpCAM positivity correlated with improved survival. These results were confirmed by (Eichelberg et al 2013) who also observed no or only weak EpCAM expression in the majority of the 767 arrayed ccRCC. Positive EpCAM IHC was significantly linked to prolonged overall survival especially in patients with localized ccRCC.…”

Reduction in Membranous Immunohistochemical Staining for the Intracellular Domain of Epithelial Cell Adhesion Molecule Correlates with Poor Patient Outcome in Primary Colorectal Adenocarcinoma

“…In breast cancer cell lines, silencing of epcam by rna interference assays has been found to reduce cell proliferation and invasion 8 . Altered epcam expression correlates with aggressive biologic behavior in stomach, breast, kidney, and thyroid carcinomas [9][10][11][12] .…”