GRIM-19、NF-κB 和 IKK2 在高级别浆液性卵巢癌患者中的预后价值。

Prognostic value of GRIM-19, NF-κB and IKK2 in patients with high-grade serous ovarian cancer.

机构信息

Laboratory of Molecular Morphology, Department of Investigative Pathology,A.C.Camargo Cancer Center, Brazil.

出版信息

Pathol Res Pract. 2018 Feb;214(2):187-194. doi: 10.1016/j.prp.2017.12.002. Epub 2017 Dec 6.

DOI:10.1016/j.prp.2017.12.002

PMID:29254797

Abstract

AIMS

High grade serous carcinoma (HGSC) is an aggressive tumour, and most patients relapse after treatment, acquiring resistance to platinum-based chemotherapy. One of the resistance mechanisms proposed is apoptosis evasion triggered by drug-related cytotoxic effect in the cell. In this context, this study aims to evaluate the protein expression of GRIM-19, NF-κB and IKK2, their association with chemotherapy response and to determine their prognostic values in HGSC.

METHODS

GRIM-19, NF-κB and IKK2 expression was evaluated by immunohistochemistry (IHC) in 71 patients with HGSC selected between 2003 and 2013, whose underwent primary debulking surgery with complete cytoreduction. Protein expression was analyzed in relation to platinum response groups, tumour progression, clinicopathological data and survival.

RESULTS

Positive IKK2 expression was related to resistance (p = 0.011), shorter disease-free survival (p = 0.001) and overall survival (p = 0.026) and was also a risk factor for relapse (p = 0.002) and death (p = 0.032). The association between IKK2 and NF-κB positivity predicted a subgroup with shorter overall survival (p = 0.004), disease-free survival (p = 0.003) and resistance to platinum-based chemotherapy (p = 0.036). NF-κB positivity was associated with worse overall survival (p = 0.005) and disease-free survival (p = 0.027) and was a positive predictor for relapse (p = 0.032) and death (p = 0.008). Higher expression of GRIM-19 was associated with higher disease-free survival (p = 0.039) and was a negative predictor for relapse (p = 0.046).

CONCLUSIONS

GRIM-19 is a potential predictor of prognosis and disease recurrence in HGSC. IKK2 and NF-κB are related to poor prognosis and are potential predictors of response to platinum-based chemotherapy in HGSC. IHC analyses of GRIM19, IKK2 and NF-κB may be important in the attempt to provide prognostic values for relapse and response to treatment in patients with HGSC.

摘要

目的

高级别浆液性癌（HGSC）是一种侵袭性肿瘤，大多数患者在治疗后复发，对铂类化疗产生耐药性。提出的耐药机制之一是药物相关细胞毒性作用触发的细胞凋亡逃逸。在这种情况下，本研究旨在评估 GRIM-19、NF-κB 和 IKK2 的蛋白表达，它们与化疗反应的关系，并确定它们在 HGSC 中的预后价值。

方法

选择 2003 年至 2013 年间接受过完全细胞减灭术的 71 例 HGSC 患者，通过免疫组织化学（IHC）评估 GRIM-19、NF-κB 和 IKK2 的表达。分析蛋白表达与铂类反应组、肿瘤进展、临床病理数据和生存的关系。

结果

IKK2 阳性表达与耐药性相关（p=0.011）、无病生存期较短（p=0.001）和总生存期较短（p=0.026），也是复发（p=0.002）和死亡（p=0.032）的危险因素。IKK2 与 NF-κB 阳性表达的相关性预测了一个总生存期（p=0.004）、无病生存期（p=0.003）和铂类化疗耐药性较短的亚组（p=0.036）。NF-κB 阳性表达与总生存期（p=0.005）和无病生存期较短（p=0.027）相关，是复发（p=0.032）和死亡（p=0.008）的阳性预测因子。GRIM-19 高表达与无病生存期较长（p=0.039）相关，是 HGSC 复发的阴性预测因子（p=0.046）。