Tissue remodelling in breast cancer: Human mast cell tryptase as an initiator of myofibroblast differentiation

Anita Mangia, Andrea Malfettone, Roberta Rossi, Angelo Paradiso, Girolamo Ranieri, Giovanni Simone, Leonardo Resta

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: Cancerogenesis is characterized by increase of differentiated myofibroblasts. Mast cells (MCs) exert powerful effects on fibroblasts through a variety of mediators. We investigated α-smooth-muscle actin (α-SMA+) and CD34+ fibroblasts, density of toluidine blue-stained (MCs-TB) and tryptase-immunolabelled MCs (MCs-Try) in 30 primary breast tumours. Methods and results: Tumour (T), peri-tumoral (PT) and non-tumoral (NT) tissue was studied by immunohistochemistry and electron microscopy. MCs-TB and MCs-Try increased gradually from NT to PT and T and the comparison between the three compartments varied significantly. Degranulated MCs were present more significantly in NT and adjacent PT than T. Transition between NT, PT and T was marked by increasing α-SMA+ fibroblasts and slow disappearance of CD34+ stromal cells. In NT, CD34+ fibroblasts correlated with low density both of MCs-TB and intact MCs-Try (P=0.0346 and P=0.0409, respectively). In T, the few preserved CD34+ fibroblasts were associated with low-density degranulated MCs-Try (P=0.0173). The α-SMA+ fibroblasts correlated with high density of intact MCs-Try in PT, and with high density of degranulated MCs-Try in T (P=0.0289), also confirmed by ultrastructural analysis. Conclusions: This preliminary investigation suggests that during breast cancer progression the MCs may contribute to stromal remodelling and differentiation of myofibroblasts, through tryptase released in stromal microenvironment.

Original languageEnglish
Pages (from-to)1096-1106
Number of pages11
JournalHistopathology
Volume58
Issue number7
DOIs
Publication statusPublished - Jun 2011

Keywords

  • α-SMA-positive myofibroblasts
  • Breast cancer
  • Toluidine blue
  • Tryptase-positive mast cells

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine

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