Molecular profiling of endometrial neoplasms reveals genetic changes in endometrial carcinomas that support the dualistic model, in which type I carcinomas are estrogen-dependent, low grade lesions and type II carcinomas are nonestrogen dependent and high grade. The molecular changes in type I endometrial carcinomas include mutations in PTEN, PIK3CA, KRAS, and β-catenin, along with microsatellite instability, whereas type II endometrial carcinomas are characterized by genetic alterations in p53, HER2/neu, p16, and E-cadherin. For endometrial neoplasms with a malignant mesenchymal component, C-MYC mutations and loss of heterozygosity are frequently seen in carcinosarcomas, and a fusion gene, JAZF1/JJAZ1, is distinctive for endometrial stromal sarcoma. In addition, p53 mutations may play an important role in tumorigenesis of undifferentiated endometrial sarcoma. These molecular changes can help in the diagnosis of endometrial neoplasms, as well as form the basis of molecular targeted therapy.
The hypercoagulability status of women with and without gynecologic malignancies was compared using the thromboelastograph coagulation analyzer. Blood specimens from 25 women with newly diagnosed gynecologic malignancies and from 21 age-matched controls were analyzed. Hypercoagulability is defined by a short R value (min), a short K value (min), an elevated maximum amplitude (MA) value (mm), and a broad alpha-angle (degrees). A two-tailed, two-sample t-test was used for statistical analysis. When compared with specimens from age-matched controls, specimens from women with gynecologic malignancies demonstrated values consistent with hypercoagulability. The specific parameters are presented as a mean (+/- SD). Patients with gynecologic malignancies were found to have a short R value (7.1 +/- 2.1 vs. 11.8 +/- 1.8 min; P < 0.001), a short K value (3.1 +/- 0.9 vs. 4.6 +/- 0.9 min; P < 0.001), a prolonged MA value (64.7 +/- 5.4 vs. 58.8 +/- 6.1 mm; P = 0.001), and a greater alpha-angle (70.6 +/- 5.3 vs. 61.6 +/- 4.9 degrees ; P < 0.001). Detection of hypercoagulability as measured by thromboelastography is statistically more common among women with gynecologic malignancies compared with age-matched controls. Future studies may address the use of thromboelastography to identify patients at risk for gynecologic malignancies.
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