Molecular Typing of Epithelial Ovarian Carcinomas Using Inflammatory Markers
Molecular Typing of Epithelial Ovarian Carcinomas Using Inflammatory Markers
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DOI：
10.1002/cncr.25588
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发表时间：
2011-01-15
期刊：
影响因子：
6.2
通讯作者：
Munkarah, Adnan R.
中科院分区：
文献类型：
--
作者：
Ali-Fehmi, Rouba;Semaan, Assaad;Munkarah, Adnan R.
背景技术背景：卵巢上皮癌最近被分类为缓慢生长的I型肿瘤和快速生长的高侵袭性II型肿瘤。本研究试图使用已知的分子标记物对I型和II型肿瘤进行分子表征。方法：采用正交设计法将213例卵巢癌患者的标本分为I型或II型，并通过免疫组织化学法评估炎症标志物葡萄糖转运蛋白-1（Glut-1）、诱导型一氧化氮合酶（iNOS）、环氧合酶-1（考克斯-1）、环氧合酶-2（考克斯-2）和核因子κ B。进行统计分析以研究这些分子标记物是否可以区分I型和II型肿瘤。Kaplan-Meier生存曲线和考克斯回归分析用于确定这些标志物对两种类型肿瘤生存的预后影响。结果：考克斯-1、考克斯-2、iNOS和Glut-1的过表达在II型肿瘤中显著增高（P <0.05）。与I型肿瘤患者（141个月）相比，II型肿瘤患者的中位生存期（60个月）较低（P=.0001）。多变量分析显示II型肿瘤、晚期和年龄>60岁是生存率差的重要预测因素。对于II型肿瘤，肿瘤过表达考克斯-2患者的中位生存期为44个月，而肿瘤低表达考克斯-2患者的中位生存期为85个月（P= 0.029）。观察I型和II型肿瘤，每个肿瘤中同时过表达的标志物数量是患者生存率差的重要预测因素（P= 0.005）。结论：目前的研究表明，新提出的卵巢上皮癌组织学分类与炎症通路蛋白的不同表达相关。这些标志物的高表达可以解释这两种肿瘤不同的生物学行为，并为治疗提供靶点。Cancer 2011; 117：301-9. (C)2010美国癌症协会
BACKGROUND: Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers. METHODS: Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein-1 (Glut-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan-Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors. RESULTS: Overexpression of COX-1, COX-2, iNOS, and Glut-1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P=.0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX-2 was 44 compared with 85 months for those with tumors with low COX-2 expression (P=.029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P=.005). CONCLUSIONS: The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy. Cancer 2011; 117: 301-9. (C) 2010 American Cancer Society.