title: Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinomas.
abstract: 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.
authors: Institute of Pathology, Charité Universitätsmedizin, Berlin, Germany.
authors: Wilko
authors: W
authors: Weichert
authors: Carsten
authors: C
authors: Denkert
authors: Aurelia
authors: A
authors: Noske
authors: Silvia
authors: S
authors: Darb-Esfahani
authors: Manfred
authors: M
authors: Dietel
authors: Steve E
authors: SE
authors: Kalloger
authors: David G
authors: DG
authors: Huntsman
authors: Martin
authors: M
authors: Köbel
mesh_terms: D018269:Carcinoma, Endometrioid / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000378:metabolism*; D011237:Predictive Value of Tests
chemical_list: D006655:Histone Deacetylases