Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas

Aurelia Noske12*, Michael Schwabe1, Wilko Weichert3, Silvia Darb-Esfahani1, Ann-Christin Buckendahl1, Jalid Sehouli4, Elena I Braicu4, Jan Budczies1, Manfred Dietel1 and Carsten Denkert1

Author Affiliations

1 Institute of Pathology, University Hospital Charité Berlin, Germany

2 Institute of Pathology, University Hospital Zurich, Switzerland

3 Institute of Pathology and National Center for Tumor Diseases, Ruprecht-Karls-Universität, Heidelberg, Germany

4 Department of Gynecology, University Hospital Charité Berlin, Germany

For all author emails, please log on.

BMC Cancer 2011, 11:294  doi:10.1186/1471-2407-11-294

Published: 14 July 2011

Abstract

Background

In ovarian cancer, the reported rate of EGFR expression varies between 4-70% depending on assessment method and data on patient outcome are conflicting. Methods: In this study we investigated EGFR expression and its prognostic value in a cohort of 121 invasive ovarian carcinomas, using a novel antibody against the intracellular domain of the receptor. We further evaluated an association between EGFR, the nuclear transporter CRM1 as well as COX-2. Furthermore, we evaluated EGFR expression in ten ovarian cancer cell lines and incubated cancer cells with Leptomycin B, a CRM1 specific inhibitor.

Results

We observed a membranous and cytoplasmic EGFR expression in 36.4% and 64% of ovarian carcinomas, respectively. Membranous EGFR was an independent prognostic factor for poor overall survival in ovarian cancer patients (HR 2.7, CI 1.1-6.4, p = 0.02) which was also found in the serous subtype (HR 4.6, CI 1.6-13.4, p = 0.004). We further observed a significant association of EGFR with COX-2 and nuclear CRM1 expression (chi-square test for trends, p = 0.006 and p = 0.013, respectively). In addition, combined membranous EGFR/COX-2 expression was significantly related to unfavorable overall survival (HR 7.2, CI 2.3-22.1, p = 0.001).

In cell culture, we observed a suppression of EGFR protein levels after exposure to Leptomycin B in OVCAR-3 and SKOV-3 cells.

Conclusions

Our results suggest that the EGFR/COX-2/CRM1 interaction might be involved in progression of ovarian cancer and patient prognosis. Hence, it is an interesting anti-cancer target for a combination therapy. Further studies will also be needed to investigate whether EGFR is also predictive for benefit from EGFR targeted therapies.

Keywords:
EGFR; CRM1; COX-2; ovarian cancer; prognosis