Michele Ammendola1, Giuseppe Currò1, Carmelo Laface2,3, Valeria Zuccalà4, Riccardo Memeo5, Francesco Luposella6, Mariarita Laforgia7, Nicola Zizzo8, Alfredo Zito9, Donato Loisi9, Rosa Patruno8, Lucia Milella1, Ippazio Ugenti1,5, Mariangela Porcelli2, Giuseppe Navarra10, Cosmo Damiano Gadaleta2, Girolamo Ranieri2. 1. Department of Health Science, Digestive Surgery Unit, Medical School, University "Magna Graecia", Viale Europa, Germaneto, 88100 Catanzaro, Italy. 2. Interventional Oncology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124 Bari, Italy. 3. Department of Biomedical Sciences and Clinical Oncology, Section of Oncology, University of Bari 'Aldo Moro', 70124 Bari, Italy. 4. Pathology Unit, "Pugliese-Ciaccio" Hospital, Viale Pio X°, 88100 Catanzaro, Italy. 5. Department of Emergency and Organ Transplantation, University Aldo Moro of Bari, 70124 Bari, Italy. 6. Direction Départementale de la Cohésion Sociale et de la Protection des Populations des VOSGES (DDCSPP88), 88080 Vittel, France. 7. Pharmacy Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124 Bari, Italy. 8. Chair of Pathology, Veterinary Medical School, University "Aldo Moro" of Bari, Via Casamassima, 70010 Bari, Italy. 9. Pathology Unit, National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Viale Orazio Flacco 65, 70124 Bari, Italy. 10. Department of Human Pathology of Adult and Evolutive Age, Surgical Oncology Division, University Hospital of Messina, 98100 Messina, Italy.
Abstract
BACKGROUND: Mast cells (MCs) contain proangiogenic factors, in particular tryptase, associated with increased angiogenesis in several tumours. With special reference to pancreatic cancer, few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue (PDAT) and adjacent normal tissue (ANT). In this study, density of mast cells positive for c-Kit receptor (MCDP-c-KitR), density of mast cells positive for tryptase (MCDPT), area of mast cells positive for tryptase (MCAPT), and angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated in a total of 45 PDAT patients with stage T2-3N0-1M0. RESULTS: For each analysed tissue parameter, the mean ± standard deviation was evaluated in both PDAT and ANT and differences were evaluated by Student's t-test (p ranged from 0.001 to 0.005). Each analysed tissue parameter was then correlated to each other one by Pearson t-test analysis (p ranged from 0.01 to 0.03). No other correlation among MCDP-c-KitR, MCDPT, MCAPT, MVD, EA and the main clinical-pathological characteristics was found. CONCLUSIONS: Our results suggest that tissue parameters increased from ANT to PDAT and that mast cells are strongly associated with angiogenesis in PDAT. On this basis, the inhibition of MCs through tyrosine kinase inhibitors, such as masitinib, or inhibition of tryptase by gabexate mesylate may become potential novel antiangiogenetic approaches in pancreatic cancer therapy.
BACKGROUND: Mast cells (MCs) contain proangiogenic factors, in particular tryptase, associated with increased angiogenesis in several tumours. With special reference to pancreatic cancer, few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue (PDAT) and adjacent normal tissue (ANT). In this study, density of mast cells positive for c-Kit receptor (MCDP-c-KitR), density of mast cells positive for tryptase (MCDPT), area of mast cells positive for tryptase (MCAPT), and angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated in a total of 45 PDAT patients with stage T2-3N0-1M0. RESULTS: For each analysed tissue parameter, the mean ± standard deviation was evaluated in both PDAT and ANT and differences were evaluated by Student's t-test (p ranged from 0.001 to 0.005). Each analysed tissue parameter was then correlated to each other one by Pearson t-test analysis (p ranged from 0.01 to 0.03). No other correlation among MCDP-c-KitR, MCDPT, MCAPT, MVD, EA and the main clinical-pathological characteristics was found. CONCLUSIONS: Our results suggest that tissue parameters increased from ANT to PDAT and that mast cells are strongly associated with angiogenesis in PDAT. On this basis, the inhibition of MCs through tyrosine kinase inhibitors, such as masitinib, or inhibition of tryptase by gabexate mesylate may become potential novel antiangiogenetic approaches in pancreatic cancer therapy.
Entities:
Keywords:
adjacent normal tissue; angiogenesis; c-Kit receptor; endothelial area; mast cells; microvascular density; pancreatic cancer tissue; tryptase