Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival
Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival
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DOI：
10.1016/j.humpath.2014.03.018
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发表时间：
2014-08-01
期刊：
影响因子：
3.3
通讯作者：
Belaud-Rotureau, Marc-Antoine
中科院分区：
文献类型：
--
作者：
Dagher, Julien;Dugay, Frederic;Belaud-Rotureau, Marc-Antoine
肾透明细胞癌(CcRCC)占肾癌的70%，临床和组织病理学因素与其预后有关。我们最近证实，PARD3基因编码的PAR-3蛋白的过度表达可能与肾脏肿瘤的发生有关。这项工作的目的是研究PAR-3在肿瘤内的表达与已知的预后参数和临床结果的关系。为此，采用免疫组织化学方法检测了2003-2005年间101例肾细胞癌患者肾癌组织中PAR-3的表达。PAR-3的免疫染色分为膜性(mPAR-3)或胞膜和胞浆(cPAR-3)。细胞质PAR-3与恶性组织病理学和临床预后因素显著相关：Fuhrman分级3~4级、肿瘤坏死、肉瘤样成分、肾上腺侵犯、肾和肺门脂肪侵犯、嗜酸性细胞成分、未失活的vhl基因、较高的肿瘤分级、淋巴结转移、较差的临床东方合作肿瘤组和S分类评分。经多因素分析，有2个参数与cPAR-3独立相关：坏死和嗜酸性成分。此外，cPAR-3患者的总生存期和无进展生存期较短，独立于强大的预后验证因素，如转移。因此，PAR-3的胞浆表达与ccRCC更差的临床和病理特征有关，并可能有助于识别高危肿瘤患者。(C)2014 Elsevier Inc.保留所有权利。
Clear cell renal cell carcinomas (ccRCCs) represent 70% of renal cancers, and several clinical and histolopathological factors are implicated in their prognosis. We recently demonstrated that the overexpression of PAR-3 protein encoded by the PARD3 gene could be implicated in renal oncogenesis. The object of this work was to study the association of intratumoral PAR-3 expression with known prognostic parameters and clinical outcome. In this aim, PAR-3 expression was assessed by immunohistochemistry in ccRCC tumors of 101 patients from 2003 to 2005. The immunostaining of PAR-3 was scored either as membranous (mPAR-3) or as both membranous and cytoplasmic (cPAR-3). Cytoplasmic PAR-3 was significantly associated with worse histopathological and clinical prognostic factors: Fuhrman grades 3 and 4, tumor necrosis, sarcomatoid component, adrenal invasion, renal and hilar fat invasion, eosinophilic component, a noninactivated VHL gene, higher tumor grade, lymph node involvement, metastasis, and worse clinical Eastern Cooperative Oncology Group and S classification scores. After multivariate analysis, 2 parameters were independently associated with cPAR-3: necrosis and eosinophilic components. In addition, cPAR-3 patients had shorter overall and progression-free survivals independently from strong prognostic validated factors like metastases. A cytoplasmic expression of PAR-3 is therefore implicated in worse clinical and pathological cancer features in ccRCC and could be useful to identify patients with high-risk tumors. (C) 2014 Elsevier Inc. All rights reserved.