Mast Cells Density Positive to Tryptase Correlate with Microvascular Density in both Primary Gastric Cancer Tissue and Loco-Regional Lymph Node Metastases from Patients That Have Undergone Radical Surgery

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.

Tumor-Associated Macrophages and Mast Cells Positive to Tryptase Are Correlated with Angiogenesis in Surgically-Treated Gastric Cancer Patients

“…To the best of our knowledge, no other study has been published regarding the concomitant assessment of both MCDPT and TAMs and neovascularization in TT and ANT from GC patients. We propose that the coupled MCDPT and TAMs could be considered as a surrogate biomarker of the degree of GC angiogenesis [ 50 , 63 , 64 , 65 ]. From a therapeutic point of view, the data obtained support a novel possibility to inhibit GC angiogenesis by targeting the coupled TAMs and MCDPTs by mean of several agents (e.g., trabectedin, peptide M2, PLX3397, STI571, AB1010).…”

Role of Mast Cells in Shaping the Tumor Microenvironment

“…[21] Tryptase-positive MCs have a role in angiogenesis in the primary tumor and in LNs of patients with metastatic GC. [22] Endometrial carcinoma An increased number of MCs were observed in different stages in which grade III showed the highest MC accumulation. Tryptase-positive MC accumulation was in correlation with angiogenesis and tumor progression.…”

Angiogenesis and Anti-Angiogenic Therapy in Gastric Cancer

“…Tryptase is stimulating proliferation of endothelial cells by activation of the proteinase-activated receptor-2 (PAR-2) [ 48 ] and VEGF is produced by this process [ 49 ]. Tryptase is mainly released by infiltrating mast cells and is thereby marking them as a potential target for the anti-angiogenic therapy in gastric cancer patients [ 50 ].…”

“…As initially described, the role of tryptase releasing mast cells in gastric cancer angiogenesis has been recently investigated. A higher density of mast cells was shown to be associated with a higher general vascularized area [ 50 ] in primary tumors and lymph node metastasis from patients undergoing resection of gastric cancer. In what way this parameter is helpful to predict survival and response to anti-angiogenic therapy has to be shown by clinical trials in the future.…”