CTNNB1 mutations and beta-catenin expression in endometrial carcinomas.
Mutations in the beta-catenin gene (CTNNB 1) with abnormal nuclear accumulation of beta-catenin have recently been identified in endometrial carcinoma (EC). Their relationship with microsatellite instability (MI) is unclear. It has been suggested that matrix metalloproteinase-7 (MMP-7) and cyclin D1 (cD) genes are targets for beta-catenin activation. DNA from 73 patients with EC was obtained from tumor and normal tissue (59 endometrioid and 14 nonendometrioid). CTNNB 1 mutations in exon 3 were assessed by single-strand conformation polymorphism and DNA sequencing. The results were correlated with immunostaining for beta-catenin, MMP-7, and cD. Three (CA)n repeats and mononucleotide tracts BAT 25 and BAT 26 had been previously used for MI analysis. CTNNB1 mutations were identified in 15 ECs (20.5%), all of them endometrioid carcinomas (15 of 59; 25.4%). They occurred in 6 of 19 MI-positive ECs (31.5%) and in 9 of 54 MI-negative ECs (16.6%). Eleven of the 15 CTNNB 1-mutated ECs showed beta-catenin nuclear immunostaining (P <.05). MMP-7 expression (>50% cells) was observed in 23 ECs, with 7 of these showing CTNNB 1 mutations. Significant expression of cD (>50% cells) was detected in 8 ECs, with 5 of these exhibiting CTNNB 1 mutations (P <.05). The results confirm that beta-catenin plays a role in endometrial carcinogenesis, particularly in endometrioid carcinomas. The results also suggest that MMP-7 and particularly cD may be targets of beta-catenin activation in ECs.
Machin
Pilar
P
Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Catasus
Lluis
L
Pons
Cristina
C
Muñoz
Josefina
J
Matias-Guiu
Xavier
X
Prat
Jaime
J
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics*; D002467:Cell Nucleus / Q000737:chemistry; D019938:Cyclin D1 / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D020783:Matrix Metalloproteinase 7 / Q000032:analysis; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; D020783:Matrix Metalloproteinase 7