Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer

Division of Hematology and Oncology, Innsbruck Medical University, Austria.
Gynecologic Oncology (Impact Factor: 3.77). 11/2006; 103(2):483-8. DOI: 10.1016/j.ygyno.2006.03.035
Source: PubMed


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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    • "Depending on the tumor type, the overexpression of EpCAM can be correlated with either increased or decreased overall survival [11]. It has been shown that higher EpCAM expression is detected in poorly differentiated human EOC and that EpCAM overexpression correlates with decreased overall survival; however , another study does not identify any impact of EpCAM overexpression on survival [15] [24]. A very recent study shows an opposite result: EpCAM overexpression is associated with better survival [14]. "
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    ABSTRACT: Although epithelial cell adhesion molecule (EpCAM) is overexpressed in human epithelial ovarian cancer (EOC), some contradictory results have been reported regarding the correlation between EpCAM overexpression and patient survival. In addition to this controversy, the function and regulation of EpCAM in EOC remain largely unknown. Here, we show that epidermal growth factor (EGF) up-regulates EpCAM expression by activating ERK1/2 signaling in a human EOC cell line, SKOV3. Additionally, EpCAM overexpression suppresses not only basal but also EGF-stimulated SKOV3 cell migration, whereas EpCAM knockdown increases both basal and EGF-stimulated cell migration in another human EOC cell line, OVCAR4. This study demonstrates the regulation of EpCAM and its role in mediating the effects of EGF on human EOC cell migration. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 01/2015; 457(3). DOI:10.1016/j.bbrc.2014.12.097 · 2.30 Impact Factor
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    • "A possible explanation could be heterogeneity clinical and histopathological characteristics of the patients. A comparison between Spizzo's collective of 199 patients and ours, showed a difference in terms of tumor stage (68% and 81.1% with FIGO stages III/IV in the collective of Spizzo compared to ours respectively) and grading (45.7% grade 3 in the study by Spizzo et al. [19] compared to 55.4% in our study), indicating that our collective was composed of more patients with advanced stages and unfavourable prognosis. Also our collective contained more patients with serous histology (40.7% and 55.4% with serous histology in the Spizzo's study and ours, respectively). "
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    ABSTRACT: Objective Epithelial cell adhesion molecule (EpCAM) has experienced a renaissance lately as a binding site for targeted therapy as well as a prognostic marker in epithelial malignancies. Aim of this study was to study EpCAM as a potential prognostic marker in epithelial ovarian cancer (EOC). Methods EpCAM expression was assessed by immunohistochemistry on paraffin-embedded primary EOC-tissue samples. EpCAM overexpression was defined as an expression of EpCAM of 76% to 100%. Tissue samples and clinical data were systematically collected within the international and multicenter "Tumorbank Ovarian Cancer" network. Results Seventy-four patients, diagnosed with EOC between 1994 and 2009, were included in the study (median age, 56 years; range, 31 to 86 years). The majority of the patients (81.1%) presented with an advanced stage International Federation of Gynecology and Obstetrics (FIGO) III/IV disease. Histology was of the serous type in 41 patients (55.4%), endometrioid in 19 (25.6%), and mucinous in 14 (19%). EpCAM was overexpressed in 87.7%. Serous tumors overexpressed EpCAM significantly more often than mucinous tumors (87.8% vs. 78.6%, p=0.045); while no significant difference was noted between the other histological subgroups. EpCAM overexpression was significantly associated with a better progression free survival and higher response rates to platinum based chemotherapy (p=0.040 and p=0.048, respectively). EpCAM was identified as an independent prognostic marker for overall survival (p=0.022). Conclusion Our data indicate a significant association of EpCAM overexpression with a more favorable survival in EOC-patients. Serous cancers showed a significant EpCAM overexpression compared to mucinous types. Larger multicenter analyses are warranted to confirm these findings.
    Journal of Gynecologic Oncology 07/2014; 25(3):221-8. DOI:10.3802/jgo.2014.25.3.221 · 2.49 Impact Factor
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    • "Furthermore, high EpCAM expression correlates with tumor grading and the prognosis of the tumors [14]–[16]. EpCAM overexpression strongly correlates with poor overall survival and bad prognosis and distinguishes patients at high risk for recurrence in a variety of cancers [9], [17], [18]. In addition, EpCAM has been demonstrated as a cancer-initiating cell marker of several solid cancers such as breast, colorectal, and pancreatic cancers [19]–[24]. "
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    ABSTRACT: Anaplastic thyroid cancer is considered to be one of the most aggressive human malignancies, and the mean survival time after diagnosis is approximately six months, regardless of treatments. This study aimed to examine how EpCAM and its related molecules are involved in the characteristics of anaplastic thyroid carcinoma. Two differentiated thyroid cancer cell lines (TPC-1 and FTC-133), and two anaplastic thyroid cancer cell lines (FRO, ACT-1) were analyzed for expression of CD44 standard isoform (CD44s), CD44 variant isoforms, and EpCAM, and human aldehyde dehydrogenase-1 (ALDH1) enzymatic activity using flow cytometry. CD44s expression was higher in TPC-1 and FTC-133 than in the FRO and ACT-1, whereas ALDH1 activities were higher in FRO and ACT-1 than in TPC-1 and FTC-133. An inverse correlation between CD44s expression and ALDH1 activity was observed in all thyroid cancer cell lines. As for the expressions of CD44 variant isoforms, ACT-1 showed higher and FRO showed moderate CD44v6 expressions, whereas either TPC-1 or FTC-133 showed negative CD44v6 expression. EpCAM expressions in FRO and ACT-1 were higher than those in TPC-1 and FTC-133, and EpCAM expressions inversely correlated with those of CD44s. A positive correlation was observed between EpCAM expression and ALDH1 activity in thyroid cancer cell lines. In the RT-PCR analysis, the expression levels of EpCAM, caludin-7 and ALDH1 in FRO and ATC-1 cells were significantly higher than those in TPC-1 and FTC-133 cells. In clinical specimens of thyroid cancers, nuclear expression of EpCAM and high expression of CD44v6 were detected significantly more frequently in anaplastic carcinomas. Our study suggests the possibility that EpCAM, together with CD44v6 and claudin-7 as well as ALDH1, may be involved in the development of the aggressive phenotype of anaplastic thyroid carcinoma. Our findings may suggest a novel therapeutic strategy for treatment of anaplastic thyroid carcinoma.
    PLoS ONE 04/2014; 9(4):e94487. DOI:10.1371/journal.pone.0094487 · 3.23 Impact Factor
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