Quantitative DNA methylation analysis of selected genes in endometrial carcinogenesis

Abstract Objective Most endometrial carcinomas appear to develop from precursors (e.g., endometrial hyperplasia) that progress for several years. Patients who are ultimately diagnosed with carcinoma often present clinically with complaints of abnormal vaginal bleeding years before diagnosis, which offers an opportunity for early diagnosis and curative treatment. The analysis of DNA methylation may be used as a method for detecting endometrial cancer (EC). To test the potential clinical application of this method, we used quantitative methylation analysis of five genes in a full spectrum of endometrial lesions. Materials and methods This hospital-based, prospective, case-controlled study was conducted on 68 patients, which included patients who had a normal endometrium ( n = 18), hyperplasia of the endometrium ( n = 24), and EC ( n = 26). Methylation levels of the following genes were determined by using real-time methylation-specific polymerase chain reaction (PCR) amplification: zinc finger protein 177 ( ZNF177 ), collagen type XIV α1 ( COL14A1 ), dihydropyrimidinase-like 4 ( DPYSL4 ), homeobox A9 ( HOXA9 ), transmembrane protein with epidermal growth factor-like and two follistatin-like domains 2 ( TMEFF2 ). The methylation index (MI) cutoff values for the different diagnoses were determined to test the sensitivity and specificity of the method and to generate the receiver operating characteristic (ROC) curves. The Mann–Whitney U test was used to test between-group differences in the MI. Results The MI of the five genes was significantly higher in EC than the MIs in specimens of hyperplasia of endometrium and normal appearance ( p