Angiogenesis in adenosquamous cancer of pancreas
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Nicola Silvestris1,*, Katia Danza2,*, Vito Longo3, Oronzo Brunetti4, Livia Fucci5, Antonella Argentiero1, Angela Calabrese6, Ivana Cataldo7, Roberto Tamma8,9, Domenico Ribatti8,9 and Stefania Tommasi2
1Medical Oncology Unit and Scientific Directorate, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124, Bari, Italy
2Molecular Genetics Laboratory, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124, Bari, Italy
3Medical Oncology Unit, Hospital “S. G. Moscati” of Taranto, 74010, Taranto, Italy
4Medical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124, Bari, Italy
5Histopatology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124, Bari, Italy
6Radiology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124, Bari, Italy
7ARC-Net Research Centre, University and Hospital Trust of Verona, 37134, Verona, Italy
8Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, 70124, Bari, Italy
9IRCCS Istituto Tumori “Giovanni Paolo II”, 70124, Bari, Italy
*These authors have contributed equally to this work
Nicola Silvestris, email: [email protected]
Keywords: angiogenesis; adenosquamous cancer of pancreas; pancreatic ductal adenocarcinoma; miRNA; micro vascular density
Received: July 14, 2017 Accepted: August 15, 2017 Published: September 27, 2017
Adenosquamous carcinoma of the pancreas (ASCP) is an uncommon variant of exocrine pancreatic malignancies, characterized by a histological admixture of adenomatous and squamous cell elements. This cancer is characterized by a poorly differentiated histology and a poorer clinical outcome compared to pancreatic ductal adenocarcinoma (PDAC). Unlike PDAC, that is characterized by a low microvascular density (MVD) and collapsed vasculature, no data are available about angiogenesis in ASPC. Immunohistochemical evaluation of MVD and trypatse-positive mast cells (MCs) were performed on a single case of ASCP compared to PDAC. Moreover, the levels of angiopoietin-1 and -2 (Ang-1, Ang-2), receptor tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2 (Tie-2), vascular endothelial growth factor A (VEGFA), hypoxia-inducible factor 1 alpha (HIF1A), miR-21-5p, miR-181a-5p, miR-122-5p, and miR-27a-3p were evaluated by real-time PCR. Higher number of tryptase-positive MCs and MVD are observed in the ASCP case compared to PDAC one. Lower levels of miR-122-5p and higher expression of VEGFA, HIF1A and Ang-2 genes were observed in ASCP. Furthermore, lower Ang-1 and Tie-2 transcript levels and higher increases of miR-21-5p, miR27a-3p and miR-181a-5p levels were found in the rarest form of pancreatic carcinoma. Our data demonstrate an important angiogenic activity in ASCP with a putative role of miR-21-5p, miR-181a-5p, miR-122-5p and miR-27a-3p in the regulation of this process.
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