Molecular pathology of endometrial hyperplasia and carcinoma.
Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-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 beta-catenin mutations do not seem to be associated with such a phenomenon.
Matias-Guiu
X
X
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
Catasus
L
L
Bussaglia
E
E
Lagarda
H
H
Garcia
A
A
Pons
C
C
Muñoz
J
J
Argüelles
R
R
Machin
P
P
Prat
J
J
D003598:Cytoskeletal Proteins / Q000235:genetics; D019175:DNA Methylation; D004714:Endometrial Hyperplasia / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human