An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-07-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1471-2407/11/294 |
| _version_ | 1828743531500404736 |
|---|---|
| author | Braicu Elena I Sehouli Jalid Buckendahl Ann-Christin Darb-Esfahani Silvia Weichert Wilko Schwabe Michael Noske Aurelia Budczies Jan Dietel Manfred Denkert Carsten |
| author_facet | Braicu Elena I Sehouli Jalid Buckendahl Ann-Christin Darb-Esfahani Silvia Weichert Wilko Schwabe Michael Noske Aurelia Budczies Jan Dietel Manfred Denkert Carsten |
| author_sort | Braicu Elena I |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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).</p> <p>In cell culture, we observed a suppression of EGFR protein levels after exposure to Leptomycin B in OVCAR-3 and SKOV-3 cells.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-04-13T01:40:08Z |
| format | Article |
| id | doaj.art-dac95b038e8a444581ce9233acbf042e |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T01:40:08Z |
| publishDate | 2011-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-dac95b038e8a444581ce9233acbf042e2022-12-22T03:08:14ZengBMCBMC Cancer1471-24072011-07-0111129410.1186/1471-2407-11-294An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomasBraicu Elena ISehouli JalidBuckendahl Ann-ChristinDarb-Esfahani SilviaWeichert WilkoSchwabe MichaelNoske AureliaBudczies JanDietel ManfredDenkert Carsten<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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).</p> <p>In cell culture, we observed a suppression of EGFR protein levels after exposure to Leptomycin B in OVCAR-3 and SKOV-3 cells.</p> <p>Conclusions</p> <p>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.</p>http://www.biomedcentral.com/1471-2407/11/294EGFRCRM1COX-2ovarian cancerprognosis |
| spellingShingle | Braicu Elena I Sehouli Jalid Buckendahl Ann-Christin Darb-Esfahani Silvia Weichert Wilko Schwabe Michael Noske Aurelia Budczies Jan Dietel Manfred Denkert Carsten An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas BMC Cancer EGFR CRM1 COX-2 ovarian cancer prognosis |
| title | An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas |
| title_full | An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas |
| title_fullStr | An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas |
| title_full_unstemmed | An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas |
| title_short | An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas |
| title_sort | intracellular targeted antibody detects egfr as an independent prognostic factor in ovarian carcinomas |
| topic | EGFR CRM1 COX-2 ovarian cancer prognosis |
| url | http://www.biomedcentral.com/1471-2407/11/294 |
| work_keys_str_mv | AT braicuelenai anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT sehoulijalid anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT buckendahlannchristin anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT darbesfahanisilvia anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT weichertwilko anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT schwabemichael anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT noskeaurelia anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT budcziesjan anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT dietelmanfred anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT denkertcarsten anintracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT braicuelenai intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT sehoulijalid intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT buckendahlannchristin intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT darbesfahanisilvia intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT weichertwilko intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT schwabemichael intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT noskeaurelia intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT budcziesjan intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT dietelmanfred intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas AT denkertcarsten intracellulartargetedantibodydetectsegfrasanindependentprognosticfactorinovariancarcinomas |