Original Article DOI: 10.1111/j.1476-5829.2009.00202.x Immunohistochemical evaluation of prostaglandin E2 and vascular endothelial growth factor in canine cutaneous mast cell tumours R. L. Amorim 1 , P. Pinczowski 2 , R. T. Neto 2 and S. C. Rahal 3 1 School of Veterinary Medicine and Animal Science, UNESP, Botucatu, S˜ ao Paulo, Brazil 2 Department of Clinical Veterinary Medicine, School of Veterinary Medicine and Animal Science, S˜ ao Paulo State University UNESP, Rubi˜ ao J ´ unior, Botucatu, S˜ ao Paulo, Brazil 3 Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, S˜ ao Paulo State University UNESP, Rubi˜ ao J ´ unior, Botucatu, S˜ ao Paulo, Brazil Abstract Vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE-2) appear to play a critical role in tumour neovascularization. In this study, we have investigated the expression of VEGF and PGE-2 in 53 canine cutaneous mast cell tumours (MCTs). Immunohistochemistry of tissue sections revealed that VEGF and PGE-2 were expressed in all mast cell tumours studied. When the expression patterns of VEGF and PGE-2 were compared with tumour grade according to Patnaik criteria, the only significant correlation observed was between PGE-2 staining intensity and tumour pathological grade, with grade II and III tumours having higher PGE-2 staining, both in intensity and percentage of cells stained, than grade I tumours (P < 0.05). Keywords angiogenesis; canine; mast cell tumour; PGE-2; VEGF Introduction Mast cell tumours (MCTs) are common cutaneous tumours in dogs. 1–4 They exhibit a range of behaviours, from virtually benign to highly invasive and metastatic. 1,3 Several investigators have applied histological grading systems to this tumour, based on the degree of differentiation. 2,4,5 Three histopathological categories were established by Patnaik et al. 4 and these histological grades correlated to survival time. The classification proposed by Patnaik. is considered to be the most complete, and thus it is the most frequently used system. 1,3 In addition to Patnaik grade, mitotic or proliferative index has proven to be a strong predictor of clinical outcome for canine MCTs. 6 Angiogenesis, the process of new blood vessel formation, is an essential component of tumour growth and metastasis. 7,8 Angiogenesis is regu- lated by a delicate balance between local pro- angiogenic and anti-angiogenic factors, which are released by both tumour and host cells, including endothelial cells, pericytes and cells of the immune system. 7,8 Many types of neoplastic cells have been shown to produce pro-angiogenic factors. Vascular endothelial growth factor (VEGF) is the prototype pro-angiogenic molecule, and it has been impli- cated in several steps in the angiogenic process. 9,10 VEGF is an endothelium-specific mitogen, which is predictive of tumour progression and recurrence in humans and dogs. 11 Mouse and human mast cells are also known to be capable of VEGF pro- duction and secretion. 12 Canine neoplastic mast cells can express both VEGF and VEGF receptors, although VEGF appears not to be an autocrine growth regulator in canine MCTs. 13 In view of Correspondence address: R. L. Amorim Department of Clinical Veterinary Medicine School of Veterinary Medicine and Animal Science S ˜ ao Paulo State University UNESP Rubi˜ ao J ´ unior 18618.000, Botucatu, S ˜ ao Paulo, Brazil e-mail: renee@fmvz.unesp.br © 2009 Universidade Estadual Paulista ‘‘Julio de mesquita Filho’’ 23