Prognostic effect of epidermal growth factor receptor gene mutations and the aberrant phosphorylation of Akt and ERK in ovarian cancer.
OBJECTIVE
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.


METHODS
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.


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).


CONCLUSIONS
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.
Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
Yoshimichi
Y
Tanaka
Yoshito
Y
Terai
Akiko
A
Tanabe
Hiroshi
H
Sasaki
Tatsuharu
T
Sekijima
Satoe
S
Fujiwara
Yoshiki
Y
Yamashita
Masanori
M
Kanemura
Masatsugu
M
Ueda
Michio
M
Sugita
Wilbur A
WA
Franklin
Masahide
M
Ohmichi
D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015999:Multivariate Analysis; D009154:Mutation; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000378:metabolism*
D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases