A gene expression signature that distinguishes desmoid tumours from nodular fasciitis

M. Bacac, E. Migliavacca, J. C. Stehle, T. McKee, M. Delorenzi, J. M. Coindre, L. Guillou, Ivan Stamenkovic

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Nodular fasciitis (NF) is a rapidly growing cellular mass composed of fibroblasts/myofibroblasts, usually localized in subcutaneous tissues, that typically undergoes fibrosis and almost never recurs. Desmoid tumours (DTs) are rare forms of fibroblastic/myofibroblastic growth that arise in deep soft tissues, display a propensity for local infiltration and recurrence, but fail to metastasize. Given that both entities are primarily fibroblastic/myofibroblastic lesions with overlapping histological features, their gene expression profiles were compared to identify differentially expressed genes that may provide not only potential diagnostic markers, but also clues as to the pathogenesis of each disorder. Differentially expressed transcripts (89 clones displaying increased expression in DTs and 246 clones displaying increased expression in NF) included genes encoding several receptor and non-receptor tyrosine kinases (EPHB3, PTPRF, GNAZ, SYK, LYN, EPHA4, BIC3), transcription factors (TWIST1, PITX2, EYA2, OAS1, MITF, TCF20), and members of the Wnt signalling pathway (AXIN2, WISP1, SFRP). Remarkably, almost one-quarter of the differentially expressed genes encode proteins associated with inflammation and tissue remodelling, including members of the interferon (IFN), tumour necrosis factor (TNF), and transforming growth factor beta (TGF-β) signalling pathways as well as metalloproteinases (MMP1, 9, 13, 23), urokinase plasminogen activator (PLAU), and cathepsins. The observations provide the first comparative molecular characterization of desmoid tumours and nodular fasciitis and suggest that selected tyrosine kinases, transcription factors, and members of the Wnt, TGF-β, IFN, and TNF signalling pathways may be implicated in influencing and distinguishing their fate.

Original languageEnglish
Pages (from-to)543-553
Number of pages11
JournalJournal of Pathology
Volume208
Issue number4
DOIs
StatePublished - Mar 2006
Externally publishedYes

Keywords

  • Desmoid tumour
  • Fibroblasts/myofibroblasts
  • Gene expression
  • Microarrays
  • Nodular fasciitis

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