Abstract
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.
Highlights
Endometrial malignancies can be categorized into two main groups based on the cell of origin: (i) endometrial carcinoma including carcinosarcoma and (ii) endometrial stromal sarcoma
There is evidence that in most carcinosarcomas, the carcinomatous and the sarcomatous components are genetically the same, as shown for 21 of 25 carcinosarcomas (84%) using the human androgen receptor (HUMARA) for detection of Xchromosome inactivation. These results support a monoclonal origin of uterine carcinosarcomas and one can hypothesize that either the sarcomatous component develops from the carcinomatous component or both are derived from a stem cell that undergoes divergent differentiation [33]
Endometrial carcinoma can be broadly divided into two categories based on clinical behavior and morphologic phenotype, with good correlation to the molecular findings
Summary
Endometrial malignancies can be categorized into two main groups based on the cell of origin: (i) endometrial carcinoma including carcinosarcoma and (ii) endometrial stromal sarcoma. Some endometrial carcinomas undergo mesenchymal differentiation and are termed carcinosarcomas (formerly termed malignant mixed mullerian tumors). The molecular alterations driving endometrial carcinogenesis may follow a sequence similar to Vogelstein’s model for the progression of colorectal adenoma to carcinoma. This process is accompanied by stepwise genetic changes of oncogenes and tumor suppressor genes. JAZF1/JJAZ1 plays a significant role in tumor development of endometrial stromal sarcomas [1]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
