title: Detection of beta-catenin mutations in paraffin-embedded sporadic desmoid-type fibromatosis by mutation-specific restriction enzyme digestion (MSRED): an ancillary diagnostic tool.
abstract: Desmoid-type fibromatosis is a locally aggressive deep soft tissue tumor. Some cases are associated with adenosis polyposis coli germline mutations whereas others harbor somatic beta-catenin point mutations mainly in exon 3, codons 41 and 45. These mutations result in stabilization of beta-catenin, and activation of the Wnt signaling pathway. The aim of this study was to determine the specificity and sensitivity of these 3 most common beta-catenin mutations in the diagnosis of desmoid-type fibromatosis using paraffin-embedded material. The results were compared with nuclear expression of beta-catenin. Mutation-specific restriction enzyme digestion methodology was employed to detect the 3 mutations. One hundred and thirty-three cases were analyzed, including 76 desmoid-type, and 18 superficial fibromatosis, in addition to a further 39 fibromatosis mimics. A restriction site was present for analysis of the codon 41 mutation. Mismatch primers were designed for the codon 45 mutations. Mutations were detected in 66 cases (87%) of 76 desmoid-type fibromatosis (71 extra-abdominal). Of these, 34 (45%) were in codon 45 (TCT>TTT), 27 (35%) in codon 41 (ACC>GCC), and 5 (7%) in codon 45 (TCT>CCT). No mutations were detected in the other lesions studied. All desmoid-type fibromatosis cases and 72% of the mimics tested showed nuclear positivity for beta-catenin indicating immunohistochemistry is a sensitive but not a specific test for desmoid-type fibromatosis. In contrast, to date, beta-catenin mutations have not been detected in any lesions which mimic desmoid-type fibromatosis. Mutation-specific restriction enzyme digestion, a simple and efficient means of detecting the common beta-catenin mutations in desmoid-type fibromatosis, complements light microscopy in reaching a diagnosis.
authors.affiliation: Department of Histopathology, Santa Casa School of Medical Sciences, Sao Paulo, Brazil.
authors.forename: Maria Fernanda C
authors.initials: MF
authors.lastname: Amary
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Els
authors.initials: E
authors.lastname: Meulemans
authors.forename: Guido M
authors.initials: GM
authors.lastname: Roemen
authors.forename: Lily
authors.initials: L
authors.lastname: Islam
authors.forename: Bernadine
authors.initials: B
authors.lastname: Idowu
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Bousdras
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Diss
authors.forename: Paul
authors.initials: P
authors.lastname: O'Donnell
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Flanagan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002467:Cell Nucleus / Q000737:chemistry; D002648:Child; D003062:Codon; D004252:DNA Mutational Analysis / Q000379:methods*; D003937:Diagnosis, Differential; D005260:Female; D018222:Desmoid Tumors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016612:Paraffin Embedding; D011237:Predictive Value of Tests; D015183:Restriction Mapping; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000032:analysis / Q000235:genetics*
chemical_list: C495270:CTNNB1 protein, human; D003062:Codon; D051176:beta Catenin