DNA methylation as a biomarker for the detection of hidden carcinoma in endometrial atypical hyperplasia

被引：31

作者：

Lai, Hung-Cheng ^{[1
,2
,3
,4
,5
,6
]}

Wang, Yu-Chi ^{[6
]}

Yu, Mu-Hsien ^{[6
]}

Huang, Rui-Lan ^{[2
]}

Yuan, Chiou-Chung ^{[1
,2
]}

Chen, Kuan-Ju ^{[7
]}

Wu, Chia-Chun ^{[8
]}

Chiang, Kai-Jo ^{[9
]}

Chao, Tai-Kuang ^{[3
]}

机构：

[1] Taipei Med Univ, Coll Med, Sch Med, Dept Obstet & Gynecol, Taipei, Taiwan

[2] Taipei Univ, Shuang Ho Hosp, Dept Obestetr & Gynecol, Taipei, Taiwan

[3] Natl Def Med Ctr, Dept & Grad Inst Biochem, Taipei, Taiwan

[4] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410008, Peoples R China

[5] Cent South Univ, Hunan Key Lab Phatmacogenet, Inst Clin Pharmacol, Changsha 410078, Peoples R China

[6] Triserv Gen Hosp, Dept Obstet & Gynecol, Natl Def Med Ctr, Taipei 114, Taiwan

[7] Triserv Gen Hosp, Dept Pathol, Natl Def Med Ctr, Taipei 114, Taiwan

[8] Triserv Gen Hosp, Dept Orthopaed Surg, Natl Def Med Ctr, Taipei 114, Taiwan

[9] Triserv Gen Hosp, Dept Nursing, Natl Def Med Ctr, Taipei 114, Taiwan

来源：

GYNECOLOGIC ONCOLOGY | 2014年 / 135卷 / 03期

关键词：

Endometrium; Atypical hyperplasia; Endometrial carcinoma; Epigenetics; Methylation; PROMOTER METHYLATION; GENES; DIAGNOSIS; IDENTIFICATION; EXPRESSION; MARKER; CANCER; CELLS; RISK;

D O I：

10.1016/j.ygyno.2014.10.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objective. Women with atypical hyperplasia (AH) are often found to have endometrial carcinoma (EC) at hysterectomy. The purpose of this study was to evaluate whether the hypermethylation of specific genes found by methylomic approaches to the study of gynecologic cancers is a biomarker for EC in women with AH. Methods. We evaluated the methylation of AJAP1, HS3ST2, SOX1, and PTGDR from 61 AH patients undergoing hysterectomy. Endometrial biopsy samples were analyzed by bisulfite conversion and quantitative methylation-specific polymerase chain reaction. A methylation index was used to predict the presence of cancer. To confirm the silencing effects of DNA methylation, immunohistochemical analysis of AJAP1, HS3ST2, and SOX1 was performed using tissue microarray. Results. Fourteen (23%) patients had EC at hysterectomy. AJAP1, HS3ST2, and SOX1 were highly methylated in the EC patients' biopsy samples (p <= 0.023). AJAP1, HS3ST2, and SOX1 protein expression was significantly higher in patients with AH only (p <= 0.038). The predictive value of AJAP1, HS3ST2, and SOX1 methylation for EC was 0.81, 0.72, and 0.70, respectively. Combined testing of both AJAP1 and HS3ST2 methylation had a positive predictive value of 56%, methylation of any one of AJAP1, SOX1, or HS3ST2 had a 100% negative predictive value. Conclusions. Hypermethylation of AJAP1, HS3ST2, and SOX1 is predictive of EC in AH patients. Testing for methylation of these genes in endometrial biopsy samples may be a hysterectomy-sparing diagnostic tool. Validation of these new genes as biomarkers for AH screening in a larger population-based study is warranted. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：552 / 559

页数：8

共 41 条

[1] DNA methylation of tumor suppressor genes in clinical remission predicts the relapse risk in acute myeloid leukemia [J].