High density of tryptase-positive mast cells in human colorectal cancer: a poor prognostic factor related to protease-activated receptor 2 expression

J Cell Mol Med. 2013 Aug;17(8):1025-37. doi: 10.1111/jcmm.12073.


Tryptase(+) mast cells (MCs), abundant in the invasive front of tumours, contribute to tissue remodelling. Indeed, protease-activated receptor-2 (PAR-2) activation by MC-tryptase is considered an oncogenic event in colorectal cancer (CRC). Recently, we have suggested NHERF1 as a potential new marker in CRC. In this study, we aimed to determine the distribution of tryptase(+) MCs and PAR-2 and to examine the relationship between PAR-2 and NHERF1, investigating their reputed usefulness as tumour markers. We studied a cohort of 115 CRC specimens including primary cancer (C) and adjacent normal mucosa (NM) by immunohistochemical double staining, analyzing the protein expression of MC-tryptase, PAR-2 and cytoplasmic NHERF1. MC density was higher in NM than in C. Tumours with high TNM stage and poor grade showed the highest MC density. A higher PAR-2 immunoreactivity characterized tumours most infiltrated by MCs compared with samples with low MC density. Furthermore, PAR-2 overexpression was associated with advanced TNM stage, poor grade and lymphovascular invasion (LVI). A positive correlation existed between tryptase(+) MC density and PAR-2 expression. Cytoplasmic NHERF1 was higher in C than in NM and overexpressing tumours resulted associated with nodal and distant metastases, poor grade and LVI. PAR-2 correlated with cytoplasmic NHERF1 and the PAR-2(+)/cytoplasmic NHERF1(+) expression immunophenotype identified tumours associated with unfavourable prognosis and aggressive clinical parameters. Our data indicate that the high density of tryptase(+) MCs at invasive margins of tumours was associated with advanced stages of CRC and was strongly correlated with PAR-2 expression.

Keywords: Colorectal cancer; NHERF1; PAR-2; aggressiveness; invasiveness; mast cell; prognostic factor; tryptase.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Count
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • Female
  • Humans
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Mast Cells / enzymology*
  • Mast Cells / pathology*
  • Middle Aged
  • Models, Biological
  • Phosphoproteins / metabolism
  • Prognosis
  • Receptor, PAR-2 / metabolism*
  • Sodium-Hydrogen Exchangers / metabolism
  • Tryptases / metabolism*


  • Phosphoproteins
  • Receptor, PAR-2
  • Sodium-Hydrogen Exchangers
  • sodium-hydrogen exchanger regulatory factor
  • Tryptases