Endometrial thickness cut-off value by transvaginal ultrasonography for screening of endometrial pathology in premenopausal and postmenopausal women

OBJECTIVE: To assess the clinical usefulness and diagnostic accuracy of ultrasonographic measurement of endometrial thickness (ET) in women with endometrial hyperplasia or cancer (EH+). METHODS: This retrospective cohort study included 29,995 consecutive women who underwent transvaginal ultrasonography (TVS) for an incidental finding of a thickened endometrium at the health screening and promotion center at Asan Medical Center between 2006 and 2010. Among 959 patients with endometrial abnormalities, 92 patients were included in this study. A total of 867 patients were excluded: 416 were lost to follow-up; 263 did not undergo endometrial biopsy; 155 had endometrial polyps; 17 had submucosal myomas; and 16 had insufficient tissue samples. Endometrial histology was the reference standard for calculating accuracy. RESULTS: Of the 92 patients, 78 (84.8%) had normal pathology, while 14 (15.2%) had endometrial pathology (EH+), including 5 patients (35.7%) with simple hyperplasia without atypia, 3 (21.4%) with complex hyperplasia, and 6 (42.9%) with endometrial carcinoma, all stage Ia. The area under the receiver-operating characteristic curve was 0.75 (95% confidence interval [CI], 0.593–0.906). The cut-off value for ET was 8 mm, indicating that TVS ET had a fair accuracy in diagnosing carcinoma, had a sensitivity of 100% (95% CI, 62.9–100.0%) and a specificity of 24.3% (95% CI, 15.2–36.3%). CONCLUSION: TVS is useful for detecting EH+, with a cut-off value for ET of 8 mm having a high sensitivity for detecting endometrial pathologies and the ability to identify women highly unlikely to have EH+, thereby avoiding more invasive endometrial biopsy.

Optimization to detect TP53 mutations in circulating cell-free tumor DNA from patients with serous epithelial ovarian cancer

OBJECTIVE: Circulating cell-free tumor DNA (cfDNA) is the DNA released by apoptotic and necrotic cells of the primary tumor into the blood during the period of tumor development. The cfDNA reflects the genetic and epigenetic alterations of the original tumor. TP53 mutations are a defining feature of high-grade serous ovarian carcinoma. We optimized the methods for detecting TP53 mutations in cfDNA from blood samples. We confirmed the correlation of TP53 mutation in primary ovarian cancer tissue and it in cfDNA using digital polymerase chain reaction (dPCR). METHODS: We found 12 frequent mutation sites in TP53 using The Cancer Genome Atlas and Catalogue of Somatic Mutations in Cancer data and manufactured 12 primers. The mutations in tissues were evaluated in fresh-frozen tissue (FFT) and formalin-fixed paraffin-embedded tissue (FFPET). We performed a prospective analysis of serial plasma samples collected from 4 patients before debulking surgery. We extracted cfDNA and calculated its concentration in blood. dPCR was used to analyze TP53 mutations in cfDNA, and we compared TP53 mutations in ovarian cancer tissue with those in cfDNA. RESULTS: Ten primers out of 12 detected the presence of TP53 mutations in FFT, FFPET, and cfDNA. In FFT and FFPET tissue, there were no significant differences. The average cfDNA concentration was 2.12±0.59 ng/mL. We also confirmed that mutations of cfDNA and those of FFT were all in R282W site. CONCLUSION: This study developed detection methods for TP53 mutations in cfDNA in ovarian cancer patients using dPCR. The results demonstrated that there are the same TP53 mutations in both ovarian cancer tissue and cfDNA.

Erratum: Correction of Acknowledgements

The Acknowledgements was published incorrectly.

Clinical characteristics of women with Mullerian anomaly: Twenty years of experience at Asan Medical Center / 대한산부인과학회지

OBJECTIVE: To investigate the clinical characteristics and reproductive outcomes of women with Mullerian anomalies. METHODS: One hundred and eighty-six patients were diagnosed with Mullerian anomalies at the Asan Medical Center from 1990 to 2009 and their clinical characteristics and reproductive outcomes were analyzed. Mullerian anomalies were categorized according to the classification by the American Fertility Society (1988). RESULTS: Mullerian anomaly was noticed in 1 in 1,326 patients (0.075%). Most cases were found in adulthood (84.9%) whereas only 15.1% cases in adolescent or pediatric period. More than 40% of cases were asymptomatic and found incidentally but others suffered from amenorrhea (12.4%), dysmenorrhea (10.8%), abnormal menstruation (10.2%), etc. Most common type of uterine anomalies was uterine didelphys (30.6%), followed by bicornuate uterus (19.4%), Mayer-Rokitansky-Kuster-Hauser syndrome (10.8%), septate uterus (9.1%) and unicornuate uterus (8.6%). On the reproductive outcomes of 251 pregnancies identified, spontaneous miscarriages and preterm labor were quite common (55.8%), and the overall live birth rate was 48.6%. When each anomaly was individually analyzed, the live birth rate was 60.0% in the arcuate uterus and 58.0% in the uterine didelphys. The unicornuate and bicornuate uterus presented a similar chance of having a living child (42.1%, 46.7%), while the septate uterus showed a relatively lower live birth rate (32.4%). CONCLUSION: Although most cases of Mullerian anomalies are diagnosed in adulthood, many patients may suffer from menstrual abnormalities, dysmenorrhea or recurrent miscarriages since adolescence. The reproductive outcomes of the arcuate uterus and uterine didelphys were better, while those of septate uterus were poor in our study.