title: Superficial fibromatoses are genetically distinct from deep fibromatoses.
abstract: Whereas deep fibromatoses (abdominal, extra-abdominal, mesenteric) display locally aggressive behavior, superficial fibromatoses typically remain small and less likely to recur despite essentially identical morphology. Somatic beta-catenin or APC gene mutations have been reported in < or =74% of sporadic deep fibromatoses and in virtually 100% of Gardner syndrome-associated fibromatoses, whereas genetic events in superficial fibromatoses remain less well characterized. We performed immunohistochemical staining for beta-catenin on 29 superficial fibromatoses (22 palmar, 5 plantar, 1 penile, and 1 infantile digital fibromatosis) and 5 deep fibromatoses. Mutations of beta-catenin and APC genes were analyzed in cases of superficial fibromatoses by direct DNA sequencing of the beta-catenin gene on Exon 3 encompassing the GSK-3 36 phosphorylation region and of the APC gene on the mutation cluster region. Nuclear accumulation of beta-catenin was present in 86% (25/29) of superficial fibromatosis cases ranging from 5 to 100% of nuclei (mean, 13%; median, 10%), though in a minority of nuclei in most examples. Deep fibromatoses had 60 to 100% nuclear staining in all five cases. No somatic mutations of beta-catenin or APC genes were identified in any of the superficial fibromatoses. In contrast to deep fibromatoses, superficial fibromatoses lack beta-catenin and APC gene mutations; the significance of focal nuclear beta-catenin accumulation is unclear. This difference may account inpart for their divergent clinical manifestations despite their morphologic resemblance to deep fibromatoses.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA. emontgom@jhmi.edu
authors.forename: E
authors.initials: E
authors.lastname: Montgomery
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: S C
authors.initials: SC
authors.lastname: Abraham
authors.forename: T T
authors.initials: TT
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D005350:Fibroma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017491:Genes, APC / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin