OBJECTIVE: We hypothesized that DNA methylation of development-related genes may occur in endometrial cancer (EC)/ovarian cancer (OC) and may be detected in cervical scrapings. METHODS: We tested methylation status by quantitative methylation-specific polymerase chain reaction for 14 genes in DNA pools of endometrial and OC tissues. Tissues of EC/normal endometrium, OC/normal ovary, were verified in training set using cervical scrapings of 10 EC/10 OC patients and 10 controls, and further validated in the testing set using independent cervical scrapings in 30 EC/30 OC patients and 30 controls. We generated cutoff values of methylation index (M-index) from cervical scrapings to distinguish between cancer patients and control. Sensitivity/specificity of DNA methylation biomarkers in detecting EC and OC was calculated. RESULTS: Of 14 genes, 4 (PTGDR, HS3ST2, POU4F3, MAGI2) showed hypermethylation in EC and OC tissues, and were verified in training set. POU4F3 and MAGI2 exhibited hypermethylation in training set were validated in independent cases. The mean M-index of POU4F3 is 78.28 in EC and 20.36 in OC, which are higher than that in controls (6.59; p<0.001 and p=0.100, respectively), and that of MAGI2 is 246.0 in EC and 12.2 in OC, which is significantly higher that than in controls (2.85; p<0.001 and p=0.480, respectively). Sensitivity and specificity of POU4F3/MAGI2 were 83%–90% and 69%–75% for detection of EC, and 61% and 62%–69% for the detection of OC. CONCLUSION: The findings demonstrate the potential of EC/OC detection through testing for DNA methylation in cervical scrapings.
Biomarkers ; DNA Methylation ; DNA ; Endometrial Neoplasms ; Endometrium ; Female ; Humans ; Methylation ; Ovarian Neoplasms ; Ovary ; Polymerase Chain Reaction ; Sensitivity and Specificity

OBJECTIVE: The malignant transformation (MT) of ovarian mature cystic teratoma (MCT) to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiple medical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, and prognostic factors of this disease and reviewed related literature. METHODS: Pathological reports of 16,001 patients with primary ovarian cancer who were treated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients with MT of MCT to SCC were identified. RESULTS: Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age of patients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40 cm). We analyzed the patients in our study and those in the literature and determined that early identification and complete surgical resection of the tumor are essential for long-term survival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be used to treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTs are suitable indicators predicting the risk of MT of MCT to SCC. CONCLUSION: Similar to general epithelial ovarian cancers, the early detection of MT of MCT to SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should be evaluated to exclude potential MT to SCC.
Carcinoma, Squamous Cell* ; Cell Transformation, Neoplastic ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Epithelial Cells* ; Humans ; Incidence ; Ovarian Neoplasms ; Taiwan ; Teratoma*

OBJECTIVE: To evaluate the clinical outcome and parameters related to coexisting endometrial carcinoma in women with tissue-diagnosed endometrial hyperplasia. METHODS: Between January 1991 and December 2009, three hundred and eighty-six patients with the presumptive diagnosis of endometrial hyperplasia were retrieved. Among these, one hundred and twenty-five patients were identified as having coexisting endometrial carcinoma in hysterectomy specimens. The three hundred and eighty-six patients were divided into two groups: the hyperplasia-benign group (261 cases) and the hyperplasia-malignant group (125 cases). Several clinical parameters including age, menopausal status, history of abnormal uterine bleeding, obstetrical history, medical history of diabetes and hypertension, BMI, and preoperative pathologic results were investigated. RESULTS: Age > or =53 (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.26 to 4.57), menopausal status (OR, 2.07; 95% CI, 1.14 to 3.76), diabetes history (OR, 7.33; 95% CI, 2.79 to 19.26), abnormal uterine bleeding (OR, 3.99; 95% CI, 1.22 to 13.02), atypical endometrial hyperplasia (OR, 7.38; 95% CI, 4.03 to 13.49), and body mass index > or =27 (OR, 3.24; 95% CI, 1.76 to 5.97) were independent risk factors for prediction of endometrial hyperplasia coexisting with endometrial carcinoma. The diagnostic efficacy of atypical endometrial hyperplasia to predict the endometrial hyperplasia coexisting with endometrial carcinoma was better than or similar to those of other independent factors and combinations of these factors. CONCLUSION: Coexisting malignancy should be considered when examining endometrial hyperplasia patients with the related risk factors, especially atypical endometrial hyperplasia.
Body Mass Index ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Female ; Humans ; Hypertension ; Hysterectomy ; Retrospective Studies ; Risk Factors ; Uterine Hemorrhage