Triage of Endometrial Atypical Hyperplasia by DNA Methylation of SOX1, HS3ST2, AJAP1 and PTGDR

• Main Authors: Chen, Kuan-Ju, 陳冠如
• Other Authors: Chao, Tai-Kuang
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/35059509426421457312

碩士 === 國防醫學院 === 病理及寄生蟲學研究所 === 100 === Endometrial carcinoma (EC) is the one of the most common cancers in female genital tract worldwide. It can be classified into two major subtypes with respect to histopathology, cell biology and clinical course. Epigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of SOX1, HS3ST2, AJAP1 and PTGDR, was evaluated in 20 endometrial carcinomas (EC) and normal endometrial tissue by methylation specific PCR. These 4 genes had higher methylation value in patients with EC than in normal controls of AJAP1, PTGDR, HS3ST2, and SOX1 (p < 0.0001, p = 0.0002, p = 0.0004, p = 0.0035, respectively). Atypical hyperplasia (AH) is a premalignant lesion of endometrial pathology. Women with this diagnosis based on endometrial sampling are frequently found to have EC at hysterectomy. The failure of accurately diagnose EC preoperatively in these women can lead to inadequate staging and potentially suboptimal treatment for some women. So, there is a need for other markers to identify women with AH in endometrial sampling harboring an underlying EC. Sixty-one endometrial sampling with pathological diagnosis of AH were analyzed. Fourteen of the sixty-one (23%) AH patients were confirmed to have EC at hysterectomy. Three of 4 genes had higher methylation value in patients with EC hidden in AH compared with AH of AJAP1, HS3ST2 and SOX1 (p = 0.0005, p = 0.014, p = 0.023, respectively). Best cutoff values of the methylation data for different genes were determined to test the sensitivity, specificity, positive predict value (PPV), negative predict value (NPV) and to generate receiver operating characteristic (ROC) curve. ROC curve analysis demonstrated that the sensitivity, specificity, accuracy, PPV and NPV for the best performance for separating EC from AH has a sensitivity of 0.86, 0.71 and 0.71, respectively, and a specificity of 0.72, 0.70 and 0.60, respectively and accuracy of 0.81, 0.72 and 0.70, respectively, and a PPV of 0.48, 0.42 and 0.35, respectively, and a NPV of 0.94, 0.89 and 0.88, respectively. In conclusion, promoter hypermethylation of AJAP1, HS3ST2, PTGDR and SOX1 is found in EC. In addition, we also show for the first time that AJAP1, HS3ST2 and SOX1 hypermethylation analysis may have potential as a EC biomarker for endometrial malignancy.