Detection of beta-catenin mutations in paraffin-embedded sporadic desmoid-type fibromatosis by mutation-specific restriction enzyme digestion (MSRED): an ancillary diagnostic tool

• Published in: The American journal of surgical pathology Vol. 31; no. 9; p. 1299
• Main Authors: Amary, Maria Fernanda C, Pauwels, Patrick, Meulemans, Els, Roemen, Guido M, Islam, Lily, Idowu, Bernadine, Bousdras, Konstantinos, Diss, Timothy C, O'Donnell, Paul, Flanagan, Adrienne M
• Format: Journal Article
• Language: English
• Published: United States 01.09.2007
• Subjects: Adolescent; Adult; Aged; Base Sequence; beta Catenin - analysis; beta Catenin - genetics; Cell Nucleus - chemistry; Child; Codon; Diagnosis, Differential; DNA Mutational Analysis - methods; Female; Fibromatosis, Aggressive - diagnosis; Fibromatosis, Aggressive - genetics; Fibromatosis, Aggressive - metabolism; Fibromatosis, Aggressive - pathology; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry - methods; Magnetic Resonance Imaging; Male; Middle Aged; Molecular Sequence Data; Mutation; Paraffin Embedding; Predictive Value of Tests; Restriction Mapping; Sensitivity and Specificity; Tissue Array Analysis
• ISSN: 0147-5185
• DOI: 10.1097/PAS.0b013e31802f581a

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.