title: Fibro-osseous lesions of the craniofacial bones: β-catenin immunohistochemical analysis and CTNNB1 and APC mutation analysis.
abstract: The canonical Wnt/β-catenin pathway is involved in the formation of craniofacial skeleton and oral tissues. Aberrant nuclear localization of β-catenin protein has been described in several human diseases including a subset of odontogenic tumors thereby suggesting an important role in tumor development. Fibro-osseous lesions of the craniofacial skeleton comprise several neoplastic, and reactive mesenchymal proliferations in which β-catenin status is unknown. To study this, we immunostained 171 fibro-osseous lesions for β-catenin protein and, for lesions with nuclear positivity, sequenced exon 3 of the CTNNB1 gene and exon 15 of the APC gene. Nuclear β-catenin immunostaining was detected in 34 (20 %) tumors with no correlation between nuclear positivity and either age, gender, or tissue decalcification status (p = 0.2, 0.17, 0.12, respectively). Absent nuclear β-catenin in fibrous dysplasia was the only diagnostically significant finding (p = 0.0034). A single point mutation at Asp56 of CTNNB1 was identified in one case of ossifying fibroma. A second ossifying fibroma and one desmoplastic fibroma demonstrated point mutations (Glu1317 and Glu1536, respectively [corrected] ) in the APC gene. These findings show that apart from fibrous dysplasia where nuclear β-catenin is rare, nuclear β-catenin staining has limited utility in discriminating among the craniofacial fibro-osseous lesions. The molecular mechanisms underlying nuclear β-catenin accumulation in the positive tumors is unlikely to be mediated by CTNNB1 exon 3 or APC exon 15 mutations in most cases.
authors.affiliation: Department of Pathology, University of California, San Francisco, 1600 Divisadero Street, B220, San Francisco, CA, 94115, USA, Andrew.horvai@ucsf.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: E Horvai
authors.forename: Richard
authors.initials: R
authors.lastname: C Jordan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001847:Bone Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005147:Facial Bones / Q000473:pathology*; D005260:Female; D017491:Genes, APC; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000473:pathology*; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin