Bibliographic Details
| Title: |
An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas |
| Authors: |
Braicu Elena I, Sehouli Jalid, Buckendahl Ann-Christin, Darb-Esfahani Silvia, Weichert Wilko, Schwabe Michael, Noske Aurelia, Budczies Jan, Dietel Manfred, Denkert Carsten |
| Source: |
BMC Cancer, Vol 11, Iss 1, p 294 (2011) |
| Publisher Information: |
BMC, 2011. |
| Publication Year: |
2011 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
EGFR, CRM1, COX-2, ovarian cancer, prognosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1471-2407 |
| Relation: |
http://www.biomedcentral.com/1471-2407/11/294; https://doaj.org/toc/1471-2407 |
| DOI: |
10.1186/1471-2407-11-294 |
| Access URL: |
https://doaj.org/article/dac95b038e8a444581ce9233acbf042e |
| Accession Number: |
edsdoj.95b038e8a444581ce9233acbf042e |
| Database: |
Directory of Open Access Journals |
