title: Frequent β-catenin gene mutations in atypical polypoid adenomyoma of the uterus.
abstract: Atypical polypoid adenomyoma (APA) is an uncommon polypoid lesion of the uterus. To clarify the mechanism of its histogenesis, we examined the functional role of β-catenin, with reference to expression of p21(waf1), cyclin D1, cyclin E, CD10, and α-smooth muscle actin (SMA), as well as cell proliferation, in 7 lesions. In the epithelial components, expression of nuclear β-catenin, p21(waf1), and cyclin D1 was increased in a stepwise fashion from normal tissue through complex atypical hyperplasia and adenomyoma to APA lesions, particularly in squamous morular areas, whereas cell proliferation, as well as cyclin E expression, was significantly decreased in the latter. Similar findings were evident in the stromal lesions, with the exception of a case of nuclear β-catenin. In addition, coexpression of CD10 and α-SMA markers was observed in the stromal components in 3 APA cases, in line with the results of normal secretory endometrial and adenomyoma samples, suggesting that cells progress to myofibromatous cells in response to differentiation-promoting events. Finally, β-catenin gene (CTNNB1) mutations were detected in all APA cases, the single nucleotide substitutions being in the epithelial but not the stromal components. These findings suggest that activation of β-catenin signaling, probably secondary to the gene abnormalities, plays an important role in the formation of the complex epithelial architecture in APAs, leading to inhibition of cell proliferation through overexpression of p21(waf1). In contrast, changes in the stromal cell phenotype may occur through a shift from CD10 to α-SMA immunopositivity, independent of CTNNB1 status.
authors.affiliation: Department of Pathology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yoshida
authors.forename: Toshihide
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tazo
authors.forename: Hisako
authors.initials: H
authors.lastname: Inoue
authors.forename: Makoto
authors.initials: M
authors.lastname: Saegusa
mesh_terms: D018194:Adenomyoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000502:physiology; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin
keywords: APA; CD10; Cyclin D1; p21(waf1); α-SMA; β-Catenin