Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer
ABSTRACT Currently available clinical and molecular factors provide still an insufficient prognostic and predictive assessment for patients with epithelial ovarian cancer (EOC). To identify a potential molecular target and prognostic/predictive factor for EOC, we investigated in a retrospective study the prognostic value of Ep-CAM overexpression in EOC.
We assessed by immunohistochemistry the expression of the Ep-CAM antigen on tissue microarrays containing paraffin-embedded tissue samples of 199 patients with documented EOC. Patients were operated for ovarian cancer in the period between June 1980 and January 2000.
We observed a rate of Ep-CAM overexpression of 68.8%. Ep-CAM overexpression was significantly related to a decreased overall survival (P = 0.036). The prognostic power of Ep-CAM overexpression was particularly strong in patients with stage III and IV disease. In fact, in this subgroup, median overall survival was twofold higher in patients without as compared to patients with Ep-CAM overexpression (46 vs. 23 months, P < 0.01). Univariate analysis revealed a correlation with histologic grade. We observed a significantly higher rate of Ep-CAM overexpression (83.5%) in grade 3 tumors. Histologic subtypes associated with a higher rate of Ep-CAM overexpression were serous carcinoma, squamous cell carcinoma, undifferentiated carcinoma, clear cell carcinoma, and endometrioid carcinoma. Cox regression analysis showed Ep-CAM overexpression to be an independent prognostic marker (P = 0.037, RR = 1.64).
This retrospective analysis demonstrates for the first time an independent prognostic value of Ep-CAM overexpression in patients with EOC. Ovarian cancer patients with Ep-CAM overexpressing tumors are frequent and would qualify for treatment with Ep-CAM-specific immunotherapeutic approaches.
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ABSTRACT: Epithelial cell adhesion molecule (EpCAM) is an epithelial and cancer cell "marker" and there is a cumulative and growing evidence of its signaling role. Its importance has been recognized as part of the breast cancer stem cell phenotype, the tumorigenic breast cancer stem cell is EpCAM(+). In spite of its complex functions in normal cell development and cancer, relatively little is known about EpCAM-interacting proteins. We used breast cancer cell lines and performed EpCAM co-immunoprecipitation followed by mass spectrometry in search for novel potentially interacting proteins. The endoplasmic reticulum aminopeptidase 2 (ERAP2) was found to co-precipitate with EpCAM and to co-localize in the cytoplasm/ER and the plasma membrane. ERAP2 is a proteolytic enzyme set in the endoplasmic reticulum (ER) where it plays a central role in the trimming of peptides for presentation by MHC class I molecules. Expression of EpCAM and ERAP2 in vitro in the presence of dog pancreas rough microsomes (ER vesicles) confirmed N-linked glycosylation, processing in ER and the size of EpCAM. The association between ERAP2 and EpCAM is a unique and novel finding that provides new ideas on EpCAM processing and on how antigen presentation may be regulated in cancer.Biochemical and Biophysical Research Communications 08/2013; 439(2). DOI:10.1016/j.bbrc.2013.08.059 · 2.28 Impact Factor
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ABSTRACT: This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.Acta biomaterialia 06/2013; 9(6):7076. DOI:10.1016/j.actbio.2010.08.010 · 5.68 Impact Factor
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ABSTRACT: BACKGROUND: The epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. The role of EpCAM is not limited to cell adhesion but includes diverse processes such as signaling, cell migration, proliferation, and differentiation. OBJECTIVE: Several studies investigated EpCAM expression in prostate carcinoma but none of them confirmed its prognostic role. The aim of our study was to investigate EpCAM expression and its relationship with established prognostic features in prostate carcinoma. MATERIALS AND METHODS: The study included a cohort of 102 patients treated with radical prostatectomy for clinically localized prostate carcinoma. Immunohistochemistry was performed to evaluate the EpCAM expression in prostate cancer and non-neoplastic prostate tissue. The percentage of positively stained carcinoma and benign glands was examined in the whole mount of the chosen slide. RESULTS: The extent of EpCAM expression was significantly higher in malignant than in benign prostatic tissue (P < 0.001). EpCAM expression in prostate cancer was associated with established features indicative of worse prognosis, such as preoperative (P = 0.009) and postoperative (P = 0.004) Gleason score and follow-up time (P < 0.001). Patients with higher preoperative and postoperative Gleason score and short follow-up time had tumors with a significantly higher expression of EpCAM. Negative correlation of follow-up time and EpCAM expression indicated that tumors in patients with biochemical recurrence (BCR) harbored higher EpCAM expression. Moreover, expression of EpCAM was significantly higher in patients with BCR compared with patients without BCR (P < 0.001). Tumors in T3 stage of the disease showed significantly higher EpCAM expression compared with T2 tumors (P = 0.002). Univariate (P < 0.001) and multivariate (P < 0.001) analyses showed that EpCAM expression was a significant predictor of shorter biochemical recurrence free-survival. CONCLUSION: Our results confirmed high level of EpCAM expression in prostate cancer and support its potential role in prostatic cancer progression. In addition, EpCAM could serve as an additional prognostic marker for the recognition of patients with an increased risk of disease recurrence that need introduction of secondary therapy.Urologic Oncology 04/2013; DOI:10.1016/j.urolonc.2011.03.007 · 3.36 Impact Factor