Molecular basis of endometrial cancer

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Abstract
Most human cancers are thought to arise from alterations in oncogenes and tumor suppressor genes. Molecular techniques have been used to identify specific genetic alterations in endometrial cancers. Overexpression of the HER-2/neu oncogene occurs in 10% of endometrial cancers and correlates with poor survival. Alterations in other receptor tyrosine kinases (c-fms and epidermal growth factor receptor) also occur in some cases. The c-myc oncogene, which encodes a nuclear transcription factor, also may be overexpressed in some invasive cancers. Mutations in the K-ras oncogene occur in 10% and in 20-30% of American and Japanese endometrial cancers, respectively. K-ras mutations also have been observed in endometrial hyperplasias, and this may represent an early event in the development of some cancers. Mutation of the p53 tumor suppressor gene, with resultant overexpression of mutant p53 protein, occurs in 20% of endometrial adenocarcinomas. Overexpression of p53 is associated with advanced stage and poor survival. Because p53 mutations do not occur frequently in endometrial hyperplasias, this may be a relatively late event in endometrial carcinogenesis. Recent studies have shown that mutations occur in microsatellite sequences in some endometrial cancers. Because microsatellite instability in hereditary nonpolyposis colon cancer has been found to be caused by mutations in DNA repair genes, similar mutations are being sought in endometrial cancers. Although several molecular alterations have been identified, the molecular pathogenesis of endometrial cancer remains poorly understood.