Mast cells positive to c-kit receptor and to tryptase in normal to cancer pancreatic tissue and the correlation with angiogenesis.

Background: In the last years published studies demonstrated that mast cells (MCs) contain pro-angiogenic factors associated with tumoral angiogenesis. Tryptase is the most abundant and potent pro-angiogenic substance contained in MCs secretory granules and it can be released in tumour microenvironment. Up to now few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma cancer tissue (PDACT) and adjacent normal tissue (ANT). Methods: In this study MCs density positive to C-Kit receptor (MCDP-C-KitR), MCs density positive to tryptase (MCDPT), MCs area positive to tryptase (MCAPT), angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated by immunohistochemistry and image analysis in both PDACT and ANT. All tissue samples were obtained from 45 patients with stage T2-3N0-1M0 (by AJCC for Pancreas Cancer Staging 7th Edition) who had undergone surgery. For each analyzed tissue parameter mean ± standard deviation was evaluated in both PDACT and ANT and differences were evaluated by Student t-test. Each analysed tissue parameter was then correlated each other by Pearson t-test analysis. Results: The mean value ± standard deviation (SD) regarding MCDP-C-KitR, MCDPT, MCAPT, MVD and EA in TT was 14.69±4.57, 13.31± 4,23, 171.41±62,39 µ2, 29.11±7.93, 201.82±70.05 µ2 respectively and the mean value ± SD in ANT was 5.61 ± 2.39, 5.13 ± 2.03, 54.43 ± 16.73 µ2, 11.45 ± 4.96, 67.60 ± 21.96 µ2, respectively. Differences in terms of mean value ± SD between PDACT and ANT were significant for each analyzed tissue biomarker (p ranged from 0,001 to 0,004 by t-test analysis; Table). Data demonstrated that MCDP-C-KitR MCDPT, MCAPT, MVD and EA significantly increased from ANT to PCT. In PCT it was showed a correlation between MCDP-C-KitR and MCDPT (r = 0.87, p = 0.01), MCDP-C-KitR and MVD (r = 0.74, p = 0.02), MCDP-C-KitR and MCAPT (r = 0.81, p = 0.01), MCDPT and MVD (r = 0.72, p = 0.02), MCD-C-KitR and EA (r = 0.73, p = 0.02), MCDPT and MCAPT (r = 0.85, p = 0.01), MCAPT and MVD (r = 0.76, p = 0.02), MCAPT and EA (r = 0.66, p = 0.03), MCDPT and EA (r = 0.69, p = 0.03), MVD and EA (r = 0.82, p = 0.01). Conclusions: Our data suggest that assessed tissue parameters increased from ANT to PDACT and that MCs are associated with angiogenesis in PDACT. On this basis inhibition of MCs by tyrosine kinase inhibitors such as masitinib or inhibition of tryptase by gabexate mesylate may be a novel antiangiogenetic approach in pancreatic cancer therapy.