Epithelial Cell Adhesion Molecule (KSA) Expression

Abstract

Purpose: Epithelial cell adhesion molecule (EpCAM) is a widely expressed adhesion molecule in epithelial cancers. The purpose of this study is to determine the protein expression patterns of EpCAM in renal cell carcinoma (RCC) using tissue arrays linked to a clinicopathological database to evaluate both its predictive power in patient stratification and its suitability as a potential target for immunotherapeutic treatment strategies.Experimental Design: The University of California, Los Angeles kidney cancer tissue microarray contains specimens from 417 patients treated with nephrectomy. EpCAM protein expression in tumors and matched morphologically normal renal tissues was evaluated using anti-EpCAM immunohistochemistry. The resultant expression reactivity was correlated with clinicopathological variables.Results: EpCAM is consistently expressed in the distal nephron on normal renal epithelium. Clear cell RCCs show minimal and infrequent EpCAM expression, whereas chromophobe and collecting duct RCCs both demonstrate intense and frequent expression. Of 318 clear cell carcinomas used in the analysis, 10% were EpCAM positive in >50% of cells, and 8% of patients would be considered candidates for EpCAM-based therapy, based on high expression [>mod-erate intensity and frequent (>50%) expression] and the need for systemic treatment. EpCAM expression was an independent prognostic factor for improved disease-specific survival, with a multivariate hazard ratio of 0.63 (P ‫؍‬ 0.017; 95% confidence interval, 0.43-0.92).Conclusions: EpCAM is a novel prognostic molecular marker in RCC patients, and its positive expression is an independent predictor associated with improved survival. However, high expression in morphologically normal renal tissues and minimal or absent expression in clear cell carcinomas will likely limit the utility of this epithelial marker in targeted treatments of this most common RCC type.

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

“…Epithelial cell adhesion molecule upregulation was an independent marker for poor survival in lymph node positive breast cancers , and gall bladder cancers (Varga et al, 2004). In contrast, improved survival was found associated with Ep-CAM upregulation in clear cell renal cell carcinoma (Kim et al, 2004;Seligson et al, 2004;Went et al, 2005), and gastric cancers (Songun et al, 2005). Here, we observed that survival of patients in the subgroup of moderately differentiated colon cancers also showed a significant positive correlation with Ep-CAM expression.…”

“…In breast and gall bladder cancer, patients with high Ep-CAMexpressing primary tumours indeed showed a decreased survival (Gastl et al, 2000;Spizzo et al, 2002;Spizzo et al, 2004;Varga et al, 2004). In clear cell renal cell carcinoma, Ep-CAM expression is infrequent, but patients with Ep-CAM overexpressing tumours show a trend to better survival (Kim et al, 2004;Seligson et al, 2004;Went et al, 2005). A similar correlation was reported for gastric cancers (Songun et al, 2005).…”

Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity

“…Some reported it was a good prognostic factor in renal cell carcinoma (Seligson et al, 2004), gastric cancer (Songun et al, 2005) and esophageal cancer (Kimura et al, 2007); while a poor prognostic factor in breast cancer (Gastl et al, 2000;Schmidt et al, 2008), gallbladder cancer (Varga et al, 2004) and esophageal cancer (Stoecklein et al, 2006). The significance of Ep-CAM expression in pancreatic cancer H Akita et al…”

“…There are some clinical reports about the relation of Ep-CAM expression to the prognosis, but the significance is uncertain; high-Ep-CAM expression was described as a good prognostic factor (Seligson et al, 2004;Songun et al, 2005;Kimura et al, 2007), while in some reports highEp-CAM expression led to poor prognosis (Gastl et al, 2000;Varga et al, 2004;Stoecklein et al, 2006). Following this discrepancy, Ep-CAM may have a different role in each type of cancer.…”

Claudin-7 Regulates EpCAM-Mediated Functions in Tumor Progression

“…The epithelial cell adhesion molecule EpCAM (EpC) is expressed on many epithelia (1, 2) and its expression is frequently increased in nearly all carcinomas as well as myelomas (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Depending on the tumor type, high EpC expression correlates with tumor grading and/or tumor-nodemetastasis staging and/or decreased overall and poor diseasefree survival (4,5,13,14).…”