Elsevier

Neoplasia

Volume 10, Issue 9, September 2008, Pages 1021-1027
Neoplasia

Expression of Class I Histone Deacetylases Indicates Poor Prognosis in Endometrioid Subtypes of Ovarian and Endometrial Carcinomas1

https://doi.org/10.1593/neo.08474Get rights and content
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open access

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.

Abbreviations

HDAC
histone deacetylase
TMA
tissue microarray
HG serous
highgrade serous

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1

This work was supported by the Cheryl Brown Ovarian Cancer Outcomes Unit of the British Columbia Cancer Agency and by an unrestricted educational grant from sanofiaventis. M.K. received fellowship support from Eli Lilly Canada.