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

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.

• Authors: Aurelia Noske, Michael Schwabe, Wilko Weichert, Silvia Darb-Esfahani, Ann-Christin Buckendahl, Jalid Sehouli, Elena I Braicu, Jan Budczies, Manfred Dietel, Carsten Denkert
• Journal: BMC cancer (BMC Cancer) Vol. 11 Pg. 294 (Jul 14 2011) ISSN: 1471-2407 [Electronic] England
• PMID: 21756326 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neoplasm
• Biomarkers, Tumor
• Fatty Acids, Unsaturated
• Karyopherins
• Neoplasm Proteins
• Receptors, Cytoplasmic and Nuclear
• exportin 1 protein
• Cyclooxygenase 2
• PTGS2 protein, human
• EGFR protein, human
• ErbB Receptors
• leptomycin B

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Antibodies, Monoclonal (immunology)
• Antibodies, Neoplasm (immunology)
• Antibody Specificity
• Biomarkers, Tumor (analysis, immunology)
• Carcinoma (chemistry, mortality, pathology)
• Cell Line, Tumor (drug effects, metabolism)
• Cohort Studies
• Cyclooxygenase 2 (analysis)
• ErbB Receptors (analysis, biosynthesis, genetics, immunology)
• Fatty Acids, Unsaturated (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Immunoenzyme Techniques
• Kaplan-Meier Estimate
• Karyopherins (analysis, antagonists & inhibitors)
• Middle Aged
• Neoplasm Proteins (analysis, antagonists & inhibitors, biosynthesis, genetics, immunology)
• Ovarian Neoplasms (chemistry, mortality, pathology)
• Prognosis
• Protein Structure, Tertiary
• Rabbits
• Receptors, Cytoplasmic and Nuclear (analysis, antagonists & inhibitors)
• Single-Blind Method