Molecular pathology of endometrial hyperplasia and carcinoma

Four different genetic abnormalities may occur in endometrioid adenocarcino mas of the endometrium (mircosatellite instability and mutations in the PTE N, k-RAS and beta -catenin genes), whereas nonendometrioid carcinomas of th e endometrium often have p53 mutations and loss of heterozygosity on severa l chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a r esult of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistoc hemical, and molecular features of the 2 types. The insaturation of microsa tellite instability in endometrial carcinogenesis seems to occur late in th e transition from complex hyperplasia to caret noma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, t he endometrioid adenocarcinomas that exhibit microsatellite instability sho w a stepwise progressive accumulation of secondary mutations in oncogenes a nd tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endo metrioid adenocarcinomas of the endometrium, particularly in the tumors tha t exhibit microsatellite instability, whereas beta -catenin mutations do no t seem to be associated nith such a phenomenon. (C) 2001 by W.B. Saunders C ompany.