MOLECULAR EVENTS IN ENDOMETRIAL CARCINOGENESIS

Progress in understanding the molecular basis of carcinogenesis will u ndoubtedly have a major impact in gynaecologic oncology. Although the details of endometrial carcinogenesis are not as yet unravelled, impor tant information has been accumulated in recent years. The identificat ion of DNA repair genes responsible for the hereditary nonpolyposis co lorectal cancer (HNPCC) and Lynch II syndromes was an important step f orward from a basic science perspective and should yield major benefit s for individuals in these families. A number of steps in sporadic end ometrial 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 bee n documented but several genetic alterations involving p53 mutation, K i-vas mutation, loss of heterozygosity (LOH) at various chromosomal lo ci and amplification/overexpression of oncogenes such as c-myc and c-n eu have been described. It is likely that as yet unknown and more freq uent genetic alterations will eventually be identified. This informati on should be available during the next decade and as a result we can a nticipate exciting progress in strategies for prevention, screening an d therapy.