Molecular events in endometrial carcinogenesis

Progress in understanding the molecular basis of carcinogenesis will undoubtedly have a major impact in gynaecologic oncology. Although the details of endometrial carcinogenesis are not as yet unravelled, important information has been accumulated in recent years. The identification of DNA repair genes responsible for the hereditary nonpolyposis colorectal cancer (HNPCC) and Lynch II syndromes was an important step forward from a basic science perspective and should yield major benefits for individuals in these families. A number of steps in sporadic endometrial carcinogenesis have now been identified and it is possible to begin to construct a speculative pathway of multistep carcinogenesis. A single frequent genetic event in endometrial cancer has not yet been documented but several genetic alterations involving p53 mutation, Ki-vas mutation, loss of heterozygosity (LOH) at various chromosomal loci and amplification/overexpression of oncogenes such as c-myc and c-neu have been described. It is likely that as yet unknown and more frequent genetic alterations will eventually be identified. This information should be available during the next decade and as a result we can anticipate exciting progress in strategies for prevention, screening and therapy.