Advances in the molecular genetics of endometrial cancer (Review)

Recent studies have identified some of the genetic alterations involved in endometrial carcinoma development. Transforming genes, including K-ras and c-erbB2/neu oncogenes and the p53, PTEN and hMLH1 tumor suppressor genes, a re the most frequently altered. In addition, endometrial carcinomas express high levels of chemoresistance markers, including the MDR-1 or the MRP gen es. The genetic background of an endometrial cancer patient may include hig h-penetrance genes such as the DNA mismatch repair genes causing microsatel lite instability, and low-penetrance genes such as those involved in estrog en-metabolism. The spectrum of several molecular lesions suggest a model fo r endometrial tumorigenesis through two divergent pathways, and which may i mprove the design of more rational therapeutic agents.