Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Br J Cancer. 2013 Sep 17;109(6):1703-10. doi: 10.1038/bjc.2013.455. Epub 2013 Aug 15.
We and others previously reported the prognostic significance of PTEN mutational status on favourable survival in endometrial carcinomas. Here, we demonstrate that loss of PTEN expression in immunohistochemistry is an independent prognostic marker for favourable survival in endometrial carcinomas.
We conducted immunohistochemical analyses of PTEN, PIK3CA, phosphorylated Akt (p-Akt), and p27 in primary endometrial carcinomas from 221 patients. Mutation of PTEN was analysed further.
Expression of PTEN was lost in 56 patients (25%), and PIK3CA was overexpressed in 159 patients (72%). Overexpression of PIK3CA was associated with p-Akt overexpression (P<0.001), which was in turn associated with loss of nuclear p27 expression (P=0.028). Loss of PTEN expression was found to be associated with endometrioid histology (P=0.03), and was inversely associated with the presence of lymphovascular space invasion (P=0.03). Univariate and multivariate survival analyses revealed that factors of PTEN loss, age <70, histological grade 1, early International Federation of Gynecology and Obstetrics (FIGO) stage, and absence of lymphovascular invasion were independent prognostic indicators for better overall survival (P=0.03, 0.04, 0.01, <0.001, and 0.03, respectively). The subset analysis showed a stronger tendency of PTEN loss towards favourable survival in advanced-stage (III and IV) disease than in early-stage (I and II) disease (P=0.05 vs 0.14). Moreover, our mutational analysis demonstrated that PTEN expression loss was associated with PTEN-truncating mutations (P=0.03).
The current observations further support the prognostic significance of PTEN aberration on favourable outcome in endometrial carcinomas, providing useful implications for the individualised management of the disease.
我们和其他人之前曾报道过，PTEN 基因突变状态对子宫内膜癌的有利生存具有预后意义。在这里，我们证明了免疫组织化学中 PTEN 表达缺失是子宫内膜癌有利生存的独立预后标志物。
我们对 221 名原发性子宫内膜癌患者进行了 PTEN、PIK3CA、磷酸化 Akt（p-Akt）和 p27 的免疫组织化学分析。进一步分析了 PTEN 的突变情况。
56 名患者（25%）的 PTEN 表达缺失，159 名患者（72%）的 PIK3CA 过表达。PIK3CA 的过表达与 p-Akt 的过表达相关（P<0.001），而后者又与核内 p27 表达缺失相关（P=0.028）。PTEN 表达缺失与子宫内膜样组织学相关（P=0.03），与淋巴血管间隙侵犯的存在呈负相关（P=0.03）。单因素和多因素生存分析显示，PTEN 缺失、年龄<70 岁、组织学分级 1 级、早期国际妇产科联合会（FIGO）分期和无淋巴血管侵犯是总生存更好的独立预后指标（P=0.03、0.04、0.01、<0.001 和 0.03）。亚组分析显示，PTEN 缺失在晚期（III 和 IV 期）疾病中对生存有利的趋势强于早期（I 和 II 期）疾病（P=0.05 与 0.14）。此外，我们的突变分析表明，PTEN 表达缺失与 PTEN 截断突变相关（P=0.03）。
目前的观察结果进一步支持了 PTEN 异常对子宫内膜癌有利结局的预后意义，为该疾病的个体化治疗提供了有用的依据。
