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.
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.
Catasús
Lluis
L
Department of Pathology, Santa Creu and Santa Pau Hospital, Autonomous University of Barcelona, Spain.
Bussaglia
Elena
E
Rodrguez
Ingrid
I
Gallardo
Alberto
A
Pons
Cristina
C
Irving
Julie A
JA
Prat
Jaime
J
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
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