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Mast cells positive to tryptase, endothelial cells positive to protease-activated receptor-2, and microvascular density correlate among themselves in hepatocellular carcinoma patients who have undergone surgery

Authors Ammendola M, Sacco R, Sammarco G, Piardi T, Zuccalà V, Patruno R, Zullo A, Zizzo N, Nardo B, Marech I, Crovace A, Gadaleta CD, Pessaux P, Ranieri G

Received 29 January 2016

Accepted for publication 24 April 2016

Published 21 July 2016 Volume 2016:9 Pages 4465—4471


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr William Cho

Michele Ammendola,1 Rosario Sacco,1 Giuseppe Sammarco,1 Tullio Piardi,2 Valeria Zuccalà,3 Rosa Patruno,4 Alessandra Zullo,1 Nicola Zizzo,4 Bruno Nardo,5 Ilaria Marech,6 Alberto Crovace,7 Cosmo Damiano Gadaleta,6 Patrick Pessaux,8 Girolamo Ranieri6

1Department of Medical and Surgical Sciences, General Surgery Unit, University of Catanzaro “Magna Graecia” Medical School, Catanzaro, Italy; 2Department of General, Digestive and Endocrine Surgery, Hopital Robert Debre, Centre Hospitalier Universitaire de Reims, Universite de Reims Champagne-Ardenne, Reims, France; 3Department of Health Science, Pathology Unit, University of Catanzaro “Magna Graecia” Medical School, Catanzaro, 4Chair of Pathology, Veterinary Medical School, University “Aldo Moro”, Bari, 5Department of Medical and Surgery Sciences, S Orsola Hospital, University of Bologna, Bologna, 6Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, “Giovanni Paolo II”, 7Department of Emergency and Organ Transplantation (DETO), Veterinary Medical School, University “Aldo Moro”, Bari, Italy; 8Hepato-Biliary and Pancreatic Surgical Unit, General, Digestive and Endocrine Surgery, IRCAD, IHU Mix-Surg, Institute for Minimally Invasive Image-Guided Surgery, University of Strasbourg, Strasbourg, France
Background: Mast cells (MCs) can stimulate angiogenesis, releasing several proangiogenic cytokines stored in their cytoplasm. In particular MCs can release tryptase, a potent in vivo and in vitro proangiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase phosphorylation. Nevertheless, no data are available concerning the relationship between MC density positive to tryptase (MCDPT), endothelial cells positive to PAR-2 forming microvascular density (PAR-2-MVD), and classical MVD (C-MVD) in hepatocellular carcinoma (HCC) angiogenesis. This study analyzed the correlation between MCDPT, PAR-2-MVD, and C-MVD, each correlated to the others and to the main clinicopathological features, in early HCC patients who underwent surgery.
Methods: A series of 53 HCC patients with early stage (stage 0 according to the Barcelona Clinic Liver Cancer Staging Classification) were selected and then underwent surgery. Tumor tissue samples were evaluated by means of immunohistochemistry and image analysis methods in terms of number of MCDPT, PAR-2-MVD, and C-MVD.
Results: A significant correlation between MCDPT, PAR-2-MVD, and C-MVD groups, each correlated to the others, was found by Pearson t-test analysis (r ranged from 0.67 to 0.81; P-value ranged from 0.01 to 0.03). No other significant correlation was found.
Conclusion: Our in vivo pilot data suggest that MCDPT and PAR-2-MVD may play a role in HCC angiogenesis and could be further evaluated as a target of antiangiogenic therapy.

Keywords: tumour angiogenesis, stromal cells, translational research

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