Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas
Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas
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DOI：
10.1593/neo.08474
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发表时间：
2008-09-01
期刊：
影响因子：
4.8
通讯作者：
Kobel, Martin
中科院分区：
文献类型：
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作者：
Weichert, Wilko;Denkert, Carsten;Kobel, Martin
组蛋白去乙酰化酶（HDAC）抑制剂是一类新兴的靶向癌症治疗剂，并且对HDAC在妇科恶性肿瘤中的表达知之甚少。因此，我们检验了1类HDAC（HDAC 1、2和3）的高水平表达是否与卵巢癌和子宫内膜癌的临床不同亚群相关的假设。通过免疫组织化学方法评估了465例卵巢癌和149例子宫内膜癌的表达，并与临床病理参数相关。每种HDAC在大多数卵巢癌（HDAC 1，61%; HDAC 2，93%; HDAC 3，84%）和子宫内膜癌（HDAC 1，61%; HDAC 2，95%; HDAC 3，83%）中均呈高水平表达。此外，55%和56%的卵巢癌和子宫内膜癌分别高水平表达所有三种HDAC。卵巢癌和子宫内膜癌的类浆液性亚型（分别为36%和52%）与高级别浆液性亚型（分别为64%和69%，P <0.001）相比，此类病例较少见。所有三种HDAC的高水平表达与卵巢恶性肿瘤的不良预后相关（风险比，6.7; 95%可信区间，1.9-23.3）。I类HDAC的独立预后信息和总体高表达率表明，这些靶点应作为卵巢癌和子宫内膜癌的预测因素进行前瞻性研究。
Histone deacetylase (HDAC) inhibitors are an emerging class of targeted cancer therapeutics, and little is known about HDAC expression in gynecologic malignancies. Therefore, we tested the hypothesis whether high-level expression of class 1 HDACs (HDAC1, 2, and 3) is associated with clinically distinct subsets of ovarian and endometrial carcinomas. Expression was assessed by immunohistochemistry in a population-based cohort of 465 ovarian and 149 endometrial carcinomas and correlated with clinicopathologic parameters. Each of the HDACs was expressed at high levels in most ovarian (HDAC1, 61%; HDAC2, 93%; HDAC3, 84%) and endometrial (HDAC1, 61%; HDAC2, 95%; HDAC3, 83%) carcinomas. Further, 55% and 56% of ovarian and endometrial carcinomas, respectively, expressed all three HDACs at high levels. Such cases were less common among endometrioid subtypes of ovarian and endometrial carcinomas (36% and 52% positive cases, respectively) compared with high-grade serous subtypes (64 and 69%, respectively, P < .001). High-level expression of all three HDACs is associated with a poor prognosis in ovarian endometrioid carcinomas (hazard ratio, 6.7; 95% confidence interval, 1.9-23.3). The independent prognostic information and the overall high rate of expression for class I HDACs suggest that these targets should be explored as predictive factors in ovarian and endometrial carcinomas prospectively.