Expression of class I histone deacetylases indicates poor prognosis in endometrioid subtypes of ovarian and endometrial carcinoma.

Wilko Weichert, Carsten Denkert, Aurelia Noske, Silvia Darb-Esfahani, Manfred Dietel, Steve E Kalloger, David G. Huntsman and Martin Kobel

Year 2008, Volume 10, Issue 9

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 if over-expression of class 1 HDAC’s (HDAC-1, 2 and 3) is associated with clinically distinct subsets of ovarian and endometrial carcinoma. Expression was assessed by immunohistochemistry in a population-based cohort of 465 ovarian and 149 endometrial carcinomas and correlated with clinicopathological parameters. Each of HDAC’s were expressed at high levels in the majority of ovarian (HDAC1 61%, HDAC2 94%, HDAC3 84%) and endometrial (HDAC1 61%, HDAC2 93%, HDAC3 85%) carcinomas. Further, 55% and 56% of ovarian and endometrial carcinomas, respectively, expressed all three HDAC’s at high levels. Such cases were less common amongst endometrioid subtypes of ovarian and endometrial carcinomas (36% and 52% positive cases, respectively) compared to high-grade serous subtypes (64 and 69%, respectively, P <0.001). High level expression of all three HDAC’s is associated with a poor prognosis in ovarian endometrioid carcinomas (HR 6.7, 95% CI 1.9 – 23.3). The independent prognostic information and the overall high rate of expression for class I HDAC’s suggests that these targets should be explored prospectively as predictive factors in ovarian and endometrial carcinomas.

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