title: PTEN mutations do not cause nuclear beta-catenin accumulation in endometrial carcinomas.
abstract: PTEN: and beta-catenin mutations constitute the predominant genetic alterations in endometrioid carcinomas of the endometrium. PTEN encodes a dual-specificity phosphatase with lipid phosphatase and protein tyrosine phosphatase activities that regulate both apoptosis and interactions with the extracellular matrix. Recent studies have associated PTEN mutations with tumorigenesis of prostate carcinoma via the Wnt signaling pathway, leading to nuclear beta-catenin accumulation. To elucidate the potential interaction of PTEN and beta-catenin in endometrial cancer, we performed mutation analyses of the entire PTEN gene and of exon 3 of the beta-catenin gene that is most frequently targeted by mutations. A total of 82 endometrial carcinomas comprising 62 type I endometrioid carcinomas and 20 type II high-grade carcinomas were investigated. In addition in a subset of 22 carcinomas, the intracellular beta-catenin distribution was analyzed by immunohistochemistry. Overall, 20 (24.4%) of 82 tumors revealed mutations in the PTEN gene, and 16 (19.5%) of 82, in the beta-catenin gene. Six tumors (7.3%) showed mutations in both the PTEN and beta-catenin gene. Mutations were mainly detected in endometrioid carcinomas of the endometrium. As expected, a striking nuclear accumulation of beta-catenin could be shown in tumors with beta-catenin mutations. In the vast majority of tumors with PTEN mutations, a regular staining pattern of the cytoplasmic and membranous compartments was found. We therefore conclude that, in contrast to prostate cancer, mutations in the PTEN gene seem not to affect cellular distribution of the beta-catenin protein in endometrial carcinomas.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospitals, Cologne, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: E
authors.initials: E
authors.lastname: Wardelmann
authors.forename: A
authors.initials: A
authors.lastname: Gehrig
authors.forename: T
authors.initials: T
authors.lastname: Schöndorf
authors.forename: N
authors.initials: N
authors.lastname: Maass
authors.forename: G
authors.initials: G
authors.lastname: Bonatz
authors.forename: A-M
authors.initials: AM
authors.lastname: Gassel
authors.forename: T
authors.initials: T
authors.lastname: Pietsch
authors.forename: P
authors.initials: P
authors.lastname: Mallmann
authors.forename: B H F
authors.initials: BH
authors.lastname: Weber
authors.forename: R K
authors.initials: RK
authors.lastname: Schmutzler
mesh_terms: D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D015534:Trans-Activators / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D051176:beta Catenin
chemical_list: 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