Abstract
Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and β-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas β-catenin mutations do not seem to be associated with such a phenomenon. Copyright © 2001 by W.B. Saunders Company.
Original language | English |
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Pages (from-to) | 569-577 |
Journal | Human Pathology |
Volume | 32 |
DOIs | |
Publication status | Published - 1 Jan 2001 |
Keywords
- Endometrial carcinoma
- MLH-1 methylation
- Microsatellite instability
- Molecular pathology
- PTEN
- k-RAS
- β-catenin