title: c-Kit expression, angiogenesis, and grading in canine mast cell tumour: a unique model to study c-Kit driven human malignancies.
abstract: Canine cutaneous mast cell tumour (CMCT) is a c-Kit driven tumour sharing similar c-Kit aberrations found in human gastrointestinal stromal tumour. CMCT is classified into three forms: well- (G1), intermediately (G2) (more benign diseases), and poorly (G3) differentiated (malignant) forms. We assess a correlation between c-Kit status, grading, and angiogenesis in CMCTs to explore their potential significance in humans. C-Kit receptor (c-KitR) expression, microvascular density (MVD), and mast cell granulated and degranulated status density (MCGD and MCDD, resp.) were analyzed in 97 CMCTs, by means of histochemistry, immunohistochemistry double staining, and image analysis system. Data showed that predominantly diffuse cytoplasmic- and predominantly focal paranuclear- (Golgi-like) c-Kit protein (PDC-c-Kit and PFP-c-Kit, resp.) expression correlate with high MVD, G3 histopathological grade, and MCDD. Moreover, predominant cell membrane-c-KitR (PCM-c-KitR) expression status correlates with low MVD, G1-G2 histopathological grade, and MCGD. These findings underline the key role of c-Kit in the biopathology of canine MCTs, indicating a link between aberrant c-Kit expression, increased angiogenesis, and higher histopathological grade. CMCT seems to be a model to study contributions of c-Kit activated MCs in tumour angiogenesis and to evaluate the inhibition of MCs activation by means of c-Kit tyrosine kinase inhibitors, currently translated in humans.
authors.affiliation: Animal Health Unit, Department of Prevention, ASL BAT, Via Andria 176, 70051 Barletta, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Patruno
authors.affiliation: Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, "Giovanni Paolo II", Via Orazio Flacco 65, 70124 Bari, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Marech
authors.affiliation: Chair of Pathology, University of Bari, Via Casamassima, 70010 Valenzano, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zizzo
authors.affiliation: Chair of Clinical Surgery, University of Catanzaro, Via Europa, 88100 Germaneto, Italy.
authors.forename: Michele
authors.identifier: 0000-0001-8043-6100
authors.initials: M
authors.lastname: Ammendola
authors.affiliation: Pharmacy Unit, National Cancer Research Centre, "Giovanni Paolo II", Via Orazio Flacco 65, 70100 Bari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nardulli
authors.affiliation: Chair of Pathology, University of Bari, Via Casamassima, 70010 Valenzano, Italy.
authors.forename: Claudia
authors.identifier: 0000-0002-1318-7834
authors.initials: C
authors.lastname: Gadaleta
authors.affiliation: Chair of Pathology, University of Bari, Via Casamassima, 70010 Valenzano, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Introna
authors.affiliation: Animal Health Unit, Department of Prevention, ASL BAT, Via Andria 176, 70051 Barletta, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Capriuolo
authors.affiliation: Animal Health Unit, Department of Prevention, ASL BAT, Via Andria 176, 70051 Barletta, Italy.
authors.forename: Rosa Angela
authors.initials: RA
authors.lastname: Rubini
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari, Piazzale Giulio Cesare 11, 70124 Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.affiliation: Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, "Giovanni Paolo II", Via Orazio Flacco 65, 70124 Bari, Italy.
authors.forename: Cosmo Damiano
authors.initials: CD
authors.lastname: Gadaleta
authors.affiliation: Interventional Radiology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre, "Giovanni Paolo II", Via Orazio Flacco 65, 70124 Bari, Italy.
authors.forename: Girolamo
authors.identifier: 0000-0001-8779-1957
authors.initials: G
authors.lastname: Ranieri
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009372:Neoplasms, Connective Tissue / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D012878:Skin Neoplasms / Q000473:pathology
chemical_list: D019009:Proto-Oncogene Proteins c-kit