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核β-连环蛋白阳性作为晚期上皮性卵巢癌长期生存的预测标志物。

Nuclear β-catenin positivity as a predictive marker of long-term survival in advanced epithelial ovarian cancer.

作者信息

Nagy Bence, Tóth László, Molnár Péter, Méhes Gábor, Thurzó László, Póka Róbert, Hernádi Zoltán

机构信息

Department of Pathology, University of Debrecen, Debrecen, Hungary; Department of Pathology, University of Szeged, Szeged, Hungary.

Department of Pathology, University of Debrecen, Debrecen, Hungary.

出版信息

Pathol Res Pract. 2017 Aug;213(8):915-921. doi: 10.1016/j.prp.2017.05.011. Epub 2017 Jun 10.

DOI:10.1016/j.prp.2017.05.011
PMID:28651933
Abstract

BACKGROUND

Classical features as histomorphology, grade, FIGO stage, and residual tumour mass have strong prognostic value in advanced epithelial ovarian carcinomas (AEOC). Most AEOCs are associated with early recurrence and poor overall survival (OS). Despite of early recurrence, general poor outcome, both high grade tumours or tumours with advanced FIGO stage at the time of diagnosis, in some of such cases, long-term survival (LTS) has been recorded . The aim of this study was to compare the utility of "classical" prognostic factors to molecular factors such as β-catenin- E-cadherin-, mutated TP53-, and MiB-1 (Ki-67) labelling index determination in predicting long-term survival.

METHODS

The expression of β-catenin, E-cadherin, Ki-67, and p53 was determined by immunohistochemistry (IHC) in AEOC. Correlation was sought for between expression of these proteins and the status of classical features vis-á-vis overall survival of patients. Statistical evaluation of the data included Kaplan-Meier analysis, the log-rank test and Cox proportional hazards model.

RESULTS

As expected, residual tumour size was an independent adverse prognostic factor for OS (univariate analysis: p=0.003, multivariate analysis: p=0.005). Nuclear expression of β-catenin in advanced ovarian cancer of LTS patients proved to be not only an independent favourable predictor of OS (univariate analysis: p=0.025, multivariate analysis: p=0.041) but also showed strong correlation with platinum sensitivity and platinum re-induction.

CONCLUSIONS

Translocation of stabilized β-catenin from cytoplasm to the nucleus plays an important role in predicting platinum sensitivity. It also seems to support the chance for platinum re-induction in AEOC and thus enhances long-term survival.

摘要

背景

组织形态学、分级、国际妇产科联盟(FIGO)分期及残留肿瘤大小等经典特征在晚期上皮性卵巢癌(AEOC)中具有很强的预后价值。大多数AEOC与早期复发及较差的总生存期(OS)相关。尽管有早期复发及总体预后较差的情况,诊断时为高级别肿瘤或FIGO分期较晚的肿瘤,在某些此类病例中仍有长期生存(LTS)的记录。本研究的目的是比较“经典”预后因素与分子因素如β-连环蛋白、E-钙黏蛋白、突变型TP53及MiB-1(Ki-67)标记指数测定在预测长期生存方面的效用。

方法

通过免疫组织化学(IHC)测定AEOC中β-连环蛋白、E-钙黏蛋白、Ki-67及p53的表达。探寻这些蛋白质的表达与经典特征状态相对于患者总生存期之间的相关性。数据的统计评估包括Kaplan-Meier分析、对数秩检验及Cox比例风险模型。

结果

正如预期,残留肿瘤大小是OS的独立不良预后因素(单变量分析:p = 0.003,多变量分析:p = 0.005)。LTS患者晚期卵巢癌中β-连环蛋白的核表达不仅被证明是OS的独立有利预测指标(单变量分析:p = 0.025,多变量分析:p = 0.041),而且与铂敏感性及铂再诱导显示出强相关性。

结论

稳定的β-连环蛋白从细胞质向细胞核的易位在预测铂敏感性中起重要作用。它似乎也支持AEOC中铂再诱导的机会,从而提高长期生存率。

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