The expression of histone deacetylase 1, but not other class I histone deacetylases, is significantly increased in endometriosis

Class I histone deacetylases (HDACs-1-3) play an important role in steroid hormone–dependent gene expression and in modulating cell survival and proliferation. We analyzed their expression in a tissue microarray including 74 endometriosis samples and 30 normal endometrium controls. The mean HDAC-1 immunoreactivity score (IRS ± standard deviation) was 7.6 ± 2.5 in endometriosis and 5.3 ± 2.3 in normal endometrium (P < .001). In contrast, the IRSs of HDAC-2 and -3 were 11.7 ± 0.7 and 11.8 ± 1.1 in endometriosis and 11.6 ± 1.0 and 11.9 ± 0.4 in normal endometrium (P = .7 and P = .2), respectively. Significant correlations were found between HDAC-1 and estrogen (-alpha/-beta) and progesterone receptor expression. In conclusion, HDAC-1, but not HDAC-2/-3, was significantly increased in endometriosis and associated with steroid hormone receptor expression that may reflect interdependence. In context with the literature, specific inhibitors of HDAC-1 may have inhibitory activities similar to those of broad-spectrum HDAC inhibitors and may be clinically tolerated, which would increase their chance as an option in the treatment of endometriosis. Similar content being viewed by others

Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447): 1789–1799. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24(2):235–258. Giudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362(25):2389–2398. Guo SW. Epigenetics of endometriosis. Mol Hum Reprod. 2009; 15(10):587–607. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J. 2003;370(pt 3): 737–749. Liu XF, Bagchi MK. Recruitment of distinct chromatin-modifying complexes by tamoxifen-complexed estrogen receptor at natural target gene promoters in vivo. J Biol Chem. 2004; 279(15):15050–15058. Suliman BA, Xu D, Williams BR. HDACi: molecular mechanisms and therapeutic implications in the innate immune system. Immunol Cell Biol. 2012;90(1):23–32. Arrowsmith CH, Bountra C, Fish PV, Lee K, Schapira M. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov. 2012;11(5):384–400. Kawano Y, Nasu K, Li H, et al. Application of the histone deacetylase inhibitors for the treatment of endometriosis: histone modifications as pathogenesis and novel therapeutic target. Hum Reprod. 2011;26(9):2486–2498. Imesch P, Fink D, Fedier A. Romidepsin reduces histone deacetylase activity, induces acetylation of histones, inhibits proliferation, and activates apoptosis in immortalized epithelial endometriotic cells. Fertil Steril. 2010;94(7):2838–2842. Imesch P, Samartzis EP, Schneider M, Fink D, Fedier A. Inhibition of transcription, expression, and secretion of the vascular epithelial growth factor in human epithelial endometriotic cells by romidepsin. Fertil Steril. 2011;95(5):1579–1583. Soares SR, Martínez-Varea A, Hidalgo-Mora JJ, Pellicer A. Pharmacologic therapies in endometriosis: a systematic review. Fertil Steril. 2012;98(3):529–555. Khan N, Jeffers M, Kumar S, et al. Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. Biochem J. 2008;409(2):581–589. Witta SE, Jotte RM, Konduri K, et al. Randomized phase II trial of erlotinib with and without entinostat in patients with advanced non-small-cell lung cancer who progressed on prior chemotherapy. J Clin Oncol. 2012;30(18):2248–2255. Samartzis N, Samartzis EP, Noske A, et al. Expression of the G protein-coupled estrogen receptor (GPER) in endometriosis: a tissue microarray study. Reprod Biol Endocrinol. 2012;10:30. Samartzis EP, Samartzis N, Noske A, et al. Loss of ARID1A/ BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation? Mod Pathol. 2012;25(6): 885–892. Samartzis N, Imesch P, Dedes KJ, et al. Expression pattern of class I histone deacetylases in vulvar intraepithelial neoplasia and vulvar cancer: a tissue microarray study. BMC Cancer. 2011;11:463. Liu X, Guo SW. A pilot study on the off-label use of valproic acid to treat adenomyosis. Fertil Steril. 2008;89(1):246–250. Liu X, Nie J, Guo SW. Elevated immunoreactivity against class I histone deacetylases in adenomyosis. Gynecol Obstet Invest. 2012;74(1):50–55. de Leval L, Waltregny D, Boniver J, Young RH, Castronovo V, Oliva E. Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus. Am J Surg Pathol. 2006;30(3):319–327. Waltregny D, De Leval L, Glénisson W, et al. Expression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues. Am J Pathol. 2004;165(2):553–564. Colón-Díaz M, Báez-Vega P, García M, et al. HDAC1 and HDAC2 are differentially expressed in endometriosis. Reprod Sci. 2012;19(5):483–492. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68(4):585–596. Bradner JE, West N, Grachan ML, et al. Chemical phylogenetics of histone deacetylases. Nat Chem Biol. 2010; 6(3):238–243. Hubbert C, Guardiola A, Shao R, et al. HDAC6 is a microtubule-associated deacetylase. Nature. 2002;417(6887):455–458. Kovacs JJ, Murphy PJ, Gaillard S, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell. 2005;18(5):601–607. Liu M, Liu X, Zhang Y, Guo SW. Valproic acid and progestin inhibit lesion growth and reduce hyperalgesia in experimentally induced endometriosis in rats. Reprod Sci. 2012;19(4): 360–373. Wu Y, Guo SW. Histone deacetylase inhibitors trichostatin A and valproic acid induce cell cycle arrest and p21 expression in immortalized human endometrial stromal cells. Eur J Obstet Gynecol Reprod Biol. 2008;137(2):198–203. Author information Authors and Affiliations Corresponding author Rights and permissions About this article Cite this article Samartzis, E.P., Noske, A., Samartzis, N. et al. The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis. Reprod. Sci. 20, 1416–1422 (2013). https://doi.org/10.1177/1933719113488450 Published: Issue date: DOI: https://doi.org/10.1177/1933719113488450