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

Tryptase(+) mast cells ( MC s), 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 NHERF 1 as a potential new marker in CRC . In this study, we aimed to determine the distribution of tryptase(+) MC s and PAR ‐2 and to examine the relationship between PAR ‐2 and NHERF 1, 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 NHERF 1. 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 MC s 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 NHERF 1 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 NHERF 1 and the PAR ‐2(+)/cytoplasmic NHERF 1(+) expression immunophenotype identified tumours associated with unfavourable prognosis and aggressive clinical parameters. Our data indicate that the high density of tryptase(+) MC s at invasive margins of tumours was associated with advanced stages of CRC and was strongly correlated with PAR ‐2 expression.