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
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 . 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  . A very recent study shows an opposite result: EpCAM overexpression is associated with better survival . "
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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.
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- "Clinical trials identified i.p. catumaxomab as a tolerable new target agent with mostly mild to moderate and reversible toxicity (pyrexia, nausea and vomiting) based on its immunological mode of action (Burges et al, 2007; Heiss et al, 2010). Epithelial cell adhesion molecule is highly expressed in EOC (Heinzelmann-Schwarz et al, 2004; Went et al, 2004) and associated with reduced survival (Spizzo et al, 2006; Woopen and Sehouli 2009). Catumaxomab is approved for the treatment of patients with symptomatic malignant ascites, a typical feature of epithelial malignancies like EOC, who are commonly presenting with peritoneal carcinomatosis. "
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This is the first study investigating the safety and efficacy of the trifunctional antibody catumaxomab administered i.p. at the end of cytoreductive surgery and postoperatively prior to standard chemotherapy in patients with primary epithelial ovarian cancer (EOC).
Patients received i.p. catumaxomab 10 μg intraoperatively and 10, 20, 50 and 150 μg on days 7, 10, 13 and 16, respectively, postoperatively. After the study, patients received standard chemotherapy and were followed for 23 months. The primary endpoint was the rate of postoperative complications.
Forty-one patients entered the study and were evaluable for safety and 34 were alive at 24 months. Complete tumour resection rate was 68%. Postoperative complications were observed in 51%, the most common anastomotic leakage (7%) and wound infections (5%). The most common catumaxomab-related adverse events were abdominal pain, nausea, vomiting and pyrexia. Thirty-nine percent discontinued catumaxomab therapy, and 98% received chemotherapy post study. Kaplan-Meier estimates of disease-free and overall survival after 24 months were 56% and 85%, respectively.
Intra- and close postoperative catumaxomab seems feasible, but efficacy and safety were limited by postsurgical complications. In the future prospective trials are needed to investigate the best schedule of integration of catumaxomab into current treatment strategies for EOC.
Available from: Hakan Mellstedt
- "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.  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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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).
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.
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).
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.
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