title: Molecular genetic alterations in endometrioid carcinomas of the ovary: similar frequency of beta-catenin abnormalities but lower rate of microsatellite instability and PTEN alterations than in uterine endometrioid carcinomas.
abstract: Endometrioid carcinomas of the ovary closely resemble their uterine counterparts. It has been suggested that the former tumors have the same molecular alterations (microsatellite instability [MSI], PTEN, and beta-catenin) described in endometrioid carcinomas of the uterus. We analyzed 55 ovarian carcinomas, including 22 endometrioid, 18 clear cell, and 15 mixed types. MSI was detected in 5 of 39 cases (13%). MLH1 promoter hypermethylation was identified in 2 of the 5 MSI-positive tumors. PTEN was mutated in 5 of 54 cases (9%); of these, 3 had MSI and exhibited frameshift mutations in short-coding mononucleotide repeats. Beta-catenin nuclear expression was detected in 11 of 54 cases (20%) by immunostaining; of these, 7 exhibited CTNNB1 gene mutations. These alterations were found more frequently in endometrioid carcinomas than in tumors of the other 2 groups. Among the former tumors, MSI was detected in 3 of 17 cases (17.5%); PTEN mutations, in 3 of 21 (14%); and beta-catenin, in 8 of 21 (38%). The molecular alterations were found more often in tumors associated with endometriosis than in tumors without endometriosis. Six endometrioid tumors demonstrating matrix metalloproteinase-7 (MMP-7) immunoreactivity with nuclear accumulation of beta-catenin had good outcomes, in contrast to poor outcomes in 7 of 9 predominantly nonendometrioid tumors demonstrating expression of MMP-7 only. We found a similar frequency of beta-catenin abnormalities but lower rates of MSI and PTEN alterations than in uterine endometrioid carcinomas. Alterations in beta-catenin and PTEN genes, as well as MSI, are frequent in low-stage ovarian carcinomas of endometrioid type that have a favorable prognosis.
authors.affiliation: Department of Pathology, Santa Creu and Santa Pau Hospital, Autonomous University of Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Catasús
authors.forename: Elena
authors.initials: E
authors.lastname: Bussaglia
authors.forename: Ingrid
authors.initials: I
authors.lastname: Rodrguez
authors.forename: Alberto
authors.initials: A
authors.lastname: Gallardo
authors.forename: Cristina
authors.initials: C
authors.lastname: Pons
authors.forename: Julie A
authors.initials: JA
authors.lastname: Irving
authors.forename: Jaime
authors.initials: J
authors.lastname: Prat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051176:beta Catenin
chemical_list: D014408:Biomarkers, Tumor; 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