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

Journal of Cellular and Molecular Medicine

Andrea Malfettone⁵  Nicola Silvestris⁴  Concetta Saponaro⁵  Girolamo Ranieri⁶  Antonio Russo³  Stefano Caruso³  Ondina Popescu²  Giovanni Simone²  Angelo Paradiso¹ 

[1] Scientific Direction, National Cancer Research Centre “Giovanni Paolo II”, Bari, Italy;Pathology Department, National Cancer Research Centre “Giovanni Paolo II”, Bari, Italy;Section of Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy;Medical Oncology Unit, National Cancer Research Centre “Giovanni Paolo II”, Bari, Italy;Functional Biomorphology Laboratory, National Cancer Research Centre “Giovanni Paolo II”, Bari, Italy;Interventional Radiology Unit, National Cancer Research Centre “Giovanni Paolo II”, Bari, Italy

关键词: Colorectal cancer;    PAR‐2;    mast cell;    tryptase;    NHERF1;    prognostic factor;    invasiveness;    aggressiveness;   

DOI  :  10.1111/jcmm.12073

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY   
© 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

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