Gatekeeper for Endometrium: the PTEN Tumor Suppressor Gene

The complexity of genetic alterations in invasive cancers and the heterogeneity of tumor cell populations hamper attempts to translate molecular understanding at the genetic level into accu- rate diagnostic and therapeutic approaches. Delineation of mo- lecular changes in the initial stages of tumor development is, therefore, highly desirable because such information can be translated into more effective cancer prevention and treatment strategies. Significant advances have been made in understand- ing the molecular events that occur as normal tissues evolve— often into precancerous lesions, some of which eventually pro- gress to cancer. In some cancers, such as colorectal carcinomas and gliomas, details of distinct molecular pathways have been identified. In most cancers, however, no consistent pattern of genetic alteration is convincingly linked to the initiation or pro- gression of the disease. In the case of endometrial cancer, molecular details are be- ginning to emerge that may eventually help advance our under- standing of the complex histopathology of this disease. Two major pathogenetic variants of endometrial carcinoma, endome- trioid and serous, seem to evolve via divergent pathways and contain distinct genetic abnormalities. Serous endometrial car- cinoma, the less common variant, is highly aggressive and es- trogen independent. More than 90% of serous tumors contain p53 mutations (1).