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细胞质中Keap1的表达与子宫内膜癌的不良预后相关。

Cytoplasmic Keap1 Expression Is Associated With Poor Prognosis in Endometrial Cancer.

作者信息

Ahtikoski Anne M, Kangas Juha, Salonen Riikka, Puistola Ulla, Karihtala Peeter

机构信息

Cancer and Translational Medicine Research Unit, Department of Pathology, Oulu University Hospital, University of Oulu, Oulu, Finland

Department of Gynecology and Obstetrics, Pedego Research Unit, Oulu University Hospital, University of Oulu, Oulu, Finland.

出版信息

Anticancer Res. 2019 Feb;39(2):585-590. doi: 10.21873/anticanres.13151.

Abstract

BACKGROUND/AIM: Oxidative stress is involved in several carcinogenic pathways. Nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1) and Park7 (DJ-1) are the main regulators of antioxidant enzymes eliminating reactive oxidative species (ROS). The roles of these proteins were studied as potential prognostic factors in endometrial cancer.

MATERIALS AND METHODS

Nrf2, Keap1 and DJ-1 expression in endometrial carcinomas was analyzed immunohistochemically. Correlations between staining patterns and clinical prognostic variables were evaluated.

RESULTS

Extensive cytoplasmic Keap1 staining correlated to several factors associated with poor prognosis of endometrial cancer including advanced stage, poor histological differentiation, lymphovascular invasion, pelvic lymph node metastasis and deep myometrial invasion. In multivariate analysis, cytoplasmic Keap1 was a stronger predictor of poor progression-free survival than grade. Nuclear Nrf2 staining was seen in all patients with lymph node metastasis while DJ-1 staining was associated with clinically favourable disease types.

CONCLUSION

Cytoplasmic Keap1 expression indicates poor prognosis in endometrial cancer.

摘要

背景/目的:氧化应激参与多种致癌途径。核因子红细胞2相关因子(Nrf2)、 Kelch样ECH相关蛋白1(Keap1)和Park7(DJ-1)是消除活性氧(ROS)的抗氧化酶的主要调节因子。研究了这些蛋白作为子宫内膜癌潜在预后因素的作用。

材料与方法

采用免疫组织化学方法分析子宫内膜癌中Nrf2、Keap1和DJ-1的表达。评估染色模式与临床预后变量之间的相关性。

结果

广泛的细胞质Keap1染色与子宫内膜癌预后不良的几个因素相关,包括晚期、组织学分化差、淋巴血管浸润、盆腔淋巴结转移和肌层深层浸润。多因素分析显示,细胞质Keap1比分级更能预测无进展生存期差。所有有淋巴结转移的患者均可见细胞核Nrf2染色,而DJ-1染色与临床预后良好的疾病类型相关。

结论

细胞质Keap1表达提示子宫内膜癌预后不良。

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