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.