Molecular pathology of atypical polypoid adenomyoma of the uterus.
Atypical polypoid adenomyoma (APA) is an uncommon and benign tumor of the uterus. In some patients, however, APA has been found to coexist with or to precede the development of an endometrioid adenocarcinoma similarly to complex endometrial hyperplasia. The molecular changes underlying the progression from APA to adenocarcinoma are unknown. DNA from paraffin-embedded tissue of 6 APAs was evaluated for microsatellite instability (MI), MLH-1 promoter hypermethylation, and CTNNB-1 mutations. Tissue sections were also subjected to MLH-1, MSH-2, and beta-catenin immunostaining. MI was not detected in any case. Two tumors exhibited MLH-1 promoter hypermethylation and showed focal negative MHL-1 immunostaining; 1 of these showed marked architectural complexity and cellular pleomorphism. Five cases presented beta-catenin nuclear immunoreactivity, but none of them had CTNNB-1 mutations. The results of this study suggest that APA and complex endometrial hyperplasia may share some molecular alterations. Some APAs exhibit MLH-1 promoter hypermethylation with focal lack of MLH-1 immunostaining, a molecular abnormality involved in the transition from complex atypical hyperplasia to endometrioid adenocarcinoma.
D048868:Adaptor Proteins, Signal Transducing; D018194:Adenomyoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D051176:beta Catenin; D000070957:MutL Protein Homolog 1