Prognostic effect of epidermal growth factor receptor gene mutations and the aberrant phosphorylation of Akt and ERK in ovarian cancer
Prognostic effect of epidermal growth factor receptor gene mutations and the aberrant phosphorylation of Akt and ERK in ovarian cancer
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DOI：
10.4161/cbt.11.1.13877
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发表时间：
2011-01-01
影响因子：
3.6
通讯作者：
Ohmichi, Masahide
中科院分区：
文献类型：
--
作者：
Tanaka, Yoshimichi;Terai, Yoshito;Ohmichi, Masahide
目的：我们在此评估了表皮生长因子受体（EGFR）基因突变对EGFR表达水平、下游介质如Akt或ERK和卵巢癌患者总生存率的影响。EGFR突变在浆液性腺癌、透明细胞腺癌和粘液性腺癌中的检出率分别为27.9%（19/68）、15.0%（3/20）和66.7%（2/3），而在类浆液性腺癌中未见突变（0/11）。EGFR、pAkt和pERK蛋白表达分别为47例（46.1%）、49例（48%）和17例（16.7%）。EGFR基因突变、EGFR和pERK表达与预后不良无关。在多变量分析中，发现高pAkt表达是无进展生存期（p = 0.017）和总生存期（p = 0.025）的显著预测因子。结论：EGFR基因突变不仅在日本人非小细胞肺癌（NSCLC）中存在，而且在日本人卵巢癌中也存在。因此，选择性EGFR抑制剂吉非替尼可能为卵巢癌EGFR突变患者提供一些益处。我们的研究结果表明Akt，但不一定是EGFR，是卵巢癌患者铂类化疗的反应和预后的最重要的靶点之一。
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.