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

Hung Cheng Lai, Yu Chi Wang, Mu Hsien Yu, Rui Lan Huang, Chiou-Chung Yuan, Kuan Ju Chen, Chia Chun Wu, Kai Jo Chiang, Tai Kuang Chao

研究成果: 雜誌貢獻文章同行評審

23 引文 斯高帕斯(Scopus)

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.
原文英語
頁(從 - 到)552-559
頁數8
期刊Gynecologic Oncology
135
發行號3
DOIs
出版狀態已發佈 - 十二月 1 2014

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology
  • Medicine(all)

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