Analysis of EphA2 expression and mutant p53 in ovarian carcinoma
Analysis of EphA2 expression and mutant p53 in ovarian carcinoma
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DOI：
10.4161/cbt.5.10.3225
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发表时间：
2006-10-01
影响因子：
3.6
通讯作者：
Sood, Anil K.
中科院分区：
文献类型：
--
作者：
Merritt, William M.;Thaker, Premal H.;Sood, Anil K.
EphA2酪氨酸激酶受体在卵巢癌中经常过度表达，这一特征预示着不良的临床结果。临床前研究也将EphA2与p53联系起来。在我们目前的研究中，我们检测了6种卵巢细胞系和79种人类卵巢癌中EphA2和p53的状态（表达和全长突变状态），以确定潜在的关联。EphA2在80%的卵巢癌细胞系和75%的临床标本中过表达。特别是，在p53零突变的肿瘤中，EphA2的高表达率为91%，而在野生型或错义突变的肿瘤中，这一比例为68% （p = 0.027）。EphA2的表达与关键位点与非关键位点错义p53突变或特定p53外显子突变的位置无关。我们还证明，虽然EphA2和p53可以提供关于临床状态的独立信息，但EphA2和p53状态的结合可以预测不良的临床预后。特别是，EphA2过表达和p53无状态的结合与患者总体生存期降低相关，并与腹水和远处转移的发生率增加相关。综上所述，这些数据表明EphA2和p53之间存在复杂的关系，这种关系似乎调节着EphA2的表达和临床结果。
The EphA2 tyrosine kinase receptor is frequently overexpressed in ovarian cancer and this feature is predictive of poor clinical outcome. Preclinical investigation has also linked EphA2 with p53. In our present study, we examined EphA2 and p53 status ( both expression and full-length mutation status) in 6 ovarian cell lines and 79 human ovarian cancers to determine potential associations. EphA2 was overexpressed in 80% of ovarian cancer cell lines and in 75% of clinical specimens. In particular, high levels of EphA2 occurred in 91% of tumors with p53 null mutations compared to 68% in tumors with wild-type or missense mutations ( p = 0.027). EphA2 expression did not relate to critical versus non-critical site missense p53 mutations or the location of mutations on specific p53 exons. We also demonstrated that while EphA2 and p53 can provide independent information regarding clinical status, the combination of EphA2 and p53 status can predict poor clinical outcome. In particular, the combination of EphA2 overexpression and p53 null status was associated with decreased overall patient survival and related to increased incidence of ascites and distant metastasis. Taken together, these data indicate a complex relationship between EphA2 and p53 that appears to regulate EphA2 expression and clinical outcome.