Immunohistochemical detection of histone deacetylases in endometrial carcinoma: involvement of histone deacetylase 2 in the proliferation of endometrial carcinoma cells

被引：26

作者：

Fakhry, Hussein ^{[2
]}

Miyamoto, Tsutomu ^{[1
]}

Kashima, Hiroyasu ^{[1
]}

Suzuki, Akihisa ^{[1
]}

Ke, He ^{[3
]}

Konishi, Ikuo ^{[4
]}

Shiozawa, Tanri ^{[1
]}

机构：

[1] Shinshu Univ, Sch Med, Dept Obstet & Gynecol, Matsumoto, Nagano 3908621, Japan

[2] Assiut Univ, S Egypt Canc Inst, Dept Surg Oncol, Assiut 7111, Egypt

[3] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Guangzhou 510080, Guangdong, Peoples R China

[4] Kyoto Univ, Fac Med, Dept Gynecol & Obstet, Kyoto 6068527, Japan

来源：

HUMAN PATHOLOGY | 2010年 / 41卷 / 06期

关键词：

Endometrial carcinoma; HDAC; Prognosis; Immunohistochemistry; SUPPRESSOR GENE-PRODUCTS; TRICHOSTATIN-A; EXPRESSION; CANCER; INHIBITORS; APOPTOSIS; APICIDIN; INDUCTION; OVARIAN; DIFFERENTIATION;

D O I：

10.1016/j.humpath.2009.11.012

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Overexpression of histone deacetylases has been reported in various human malignancies; however, the expression of histone deacetylases in endometrial tissue is not fully understood. In the present study, the expression of histone deacetylase 1, histone deacetylase 2, and Ki-67 was examined immunohistochemically in 30 normal and 66 malignant endometrial tissue samples. The results were expressed as a positivity index and compared with the positivity index for Ki-67 and rates of patient survival. The effect of 2 histone deacetylase inhibitors, trichostatin A and apicidine, on cell proliferation and the expression of cell cycle regulators such as cyclins (D1, E, and A), p21, p27, and p16 were investigated using 6 endometrial carcinoma cell lines. The positivity index for histone deacetylase I (79.8 +/- 33.0, mean +/-SD) and histone deacetylase 2 (106.3 +/- 41.9) was higher in endometrial carcinoma than the normal endometrium, with a significant difference for histone deacetylase 2. The positivity index for histone deacetylase 2 was significantly increased in higher-grade carcinomas (positivity index for grade 3, 124.9 +/- 28.4) compared with grade 1 tumors (86.0 +/- 41.0) and was positively correlated with that for Ki-67. In addition, patients with histone deacetylase 2 positive carcinomas had a poor prognosis compared with those with histone deacetylase 2 negative carcinoma (P = .048). Treatment with trichostatin A or apicidine suppressed the proliferation in all cell lines examined, in association with increased expression of p21 and down-regulation of cyclin D1 and cyclin A expression. These results indicated that increased histone deacetylase 2 expression is involved in the acquisition of aggressive behavior by endometrial carcinoma and suggest histone deacetylase inhibitor to be a promising anticancer drug for this carcinoma. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：848 / 858

页数：11

共 37 条

[1] Mechanism of apicidin-induced cell cycle arrest and apoptosis in Ishikawa human endometrial cancer cells [J].