Abstract

Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases. A series of 75 GC patients with stage T2–3N2–3M0 (by AJCC for Gastric Cancer Seventh Edition) undergone to radical surgery were selected for the study. MCDPT and MVD were evaluated by immunohistochemistry and by image analysis system and results were correlated each to other in primary tumor tissue and in metastatic lymph nodes harvested. Furthermore, tissue parameters were correlated with important clinico-pathological features. A significant correlation between MCDPT and MVD was found in primary gastric cancer tissue and lymph node metastases. Pearson t-test analysis (r ranged from 0.74 to 0.79; p-value ranged from 0.001 to 0.003). These preliminary data suggest that MCDPT play a role in angiogenesis in both primary tumor and in lymph node metastases from GC. We suggest that MCs and tryptase could be further evaluated as novel targets for anti-angiogenic therapies.

Highlights

  • Mast Cells (MCs) can play a role in tumor angiogenesis and their involvement has been demonstrated in several animal and human malignancies [1,2]

  • From a biological point of view, the signalling induced by tryptase can be mediated via protease-activated receptor-2 (PAR-2) expressed on ECs, that in turn lead to ECs proliferation forming angiogenesis [9–27]

  • Few data have been published on the relationship among MCs density positive to tryptase (MCDPT), and microvascular density (MVD) in both primary gastric cancer (GC) tissue and loco-regional lymph node metastases (LRLNM) [6,28–32]

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Summary

Introduction

Mast Cells (MCs) can play a role in tumor angiogenesis and their involvement has been demonstrated in several animal and human malignancies [1,2]. From a biological point of view, the signalling induced by tryptase can be mediated via protease-activated receptor-2 (PAR-2) expressed on ECs, that in turn lead to ECs proliferation forming angiogenesis [9–27]. In GC, the presence of lymph node metastases is one of the most important determinants of prognosis and tumor node metastases (TNM) is the most commonly used staging system [33]. In this pilot study, we analyzed by immunohistochemistry and image analysis system MCDPT and MVD in both primary GC tumor tissue (PGCTT) and LRLNM from 75 patients undergoing radical surgery. The correlation between the studied parameters and the main clinico-pathological features has been performed

Results
Study Population
Immunohistochemistry
Morphometrical Assay
Statistical Analysis

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