Journal
CANCER BIOLOGY & THERAPY
Volume 11, Issue 1, Pages 50-57Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.11.1.13877
Keywords
ovarian cancer; EGFR mutation; pAkt; pERK; EGFR protein; gefitinib; platinum; immunohistochemistry; prognostic factor
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [19591946]
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Objectives: We herein assessed the influence of Epidermal Growth Factor Receptor (EGFR) gene mutations on EGFR expression levels, downstream mediators such as Akt or ERK and overall survival in patients with ovarian cancer. Results: Twenty-nine EGFR gene mutations were detected in 24 of 102 patinets (23.5%). EGFR mutations were observed in 27.9% (19/68) in serous adenocarcinomas, 15.0% (3/20) in clear cell adenocarcinomas and 66.7% (2/3) in mucinous adenocarcinomas, while no mutations were observed in endometrioid adenocarcinomas (0/11). Protein expression of EGFR, pAkt and pERK were detected in 47 (46.1%), 49 (48%) and 17 (16.7%) of patients, respectively. EGFR gene mutations, EGFR and pERK expression were not associated with a poor prognosis. In a multivariate analysis, a High pAkt expression was found to be a significant predictor for both the progression free survival (p = 0.017) and overall survival (p = 0.025). Study Design: EGFR mutation status was analyzed by direct sequencing in 102 Japanese ovarian cancer patients. The EGFR expression, phosphorylated Akt (pAkt) and phosphorylated ERK (pERK) were determined by immunohistochemistry. Conclusion: EGFR gene mutations were frequently observed in not only non-small-cell lung cancer (NSCLC), but also in ovarian cancer in Japanese patients. The selective EGFR inhibitor Gefitinib might therefore offer some benefit in patients with EGFR mutations in ovarian cancer. Our results indicate that the Akt, but not necessarily EGFR, is one of the most important target in the response of the platinum-based chemotherapy and prognosis for ovarian cancer patients.
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