Fibro-Osseous Lesions of the Craniofacial Bones: ß-Catenin Immunohistochemical Analysis and CTNNB1 and APC Mutation Analysis.

Head and Neck Pathology

PubMedID: 24664543

E Horvai A, C Jordan R. Fibro-Osseous Lesions of the Craniofacial Bones: ß-Catenin Immunohistochemical Analysis and CTNNB1 and APC Mutation Analysis. Head Neck Pathol. 2014;8(3):291-7.
The canonical Wnt/ß-catenin pathway is involved in the formation of craniofacial skeleton and oral tissues. Aberrant nuclear localization of ß-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 ß-catenin status is unknown. To study this, we immunostained 171 fibro-osseous lesions for ß-catenin protein and, for lesions with nuclear positivity, sequenced exon 3 of the CTNNB1 gene and exon 15 of the APC gene. Nuclear ß-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 ß-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 (Glu1229 and Tyr1475, respectively) in the APC gene. These findings show that apart from fibrous dysplasia where nuclear ß-catenin is rare, nuclear ß-catenin staining has limited utility in discriminating among the craniofacial fibro-osseous lesions. The molecular mechanisms underlying nuclear ß-catenin accumulation in the positive tumors is unlikely to be mediated by CTNNB1 exon 3 or APC exon 15 mutations in most cases.