Canine cutaneous mast cell tumor: diagnosis and prognosis
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Published:
Jul 11, 2018
Keywords:
Mast cell tumor Histochemistry Immunohistochemistry Diagnosis Prognostic indicator Canine
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Abstract
Mast cell tumors are the most common skin tumors of dog. Their appearance and biological behavior are variable, leading to frequent failure in treatment. Most mast cell tumors are routinely diagnosed by cytological and histological examination base on their morphological and staining characteristics. Others histochemical staining can give more information about their specific staining and enzyme activity. However, poorly differentiated mast cell tumors can be confused with other round cell tumors. Misdiagnosis and failure to identify the tumors might be circumstance. Immunohistochemistry has been used as an adjunct in the diagnosis and prognosis of neoplasms, including mast cell tumors. This article reviews the features of canine cutaneous mast cell tumors, as well as various histochemical and immunohistochemical stains used for their capability to diagnosis and prognosis. Together with clinical information and other prognostic indicators, these will support treatment planning and tumor monitoring properly.
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Review Article
References
Abraham, S.N. and Malaviya, R. 1997. Mast cells in infection and immunity. Infect. Immun. 65: 3501-3508.
Bancroft, J. and Gamble, M. 2008. Theory and Practice of Histological Techniques. 6th ed. Churchill Livingstone/Elsevier, Philadelphia. 725 p.
Beaven, M.A. and Metzger, H. 1993. Signal transduction by Fc receptors: the Fc epsilon RI case. Immunol. Today 14(5): 222-226.
De Souza Junior, D.A., Santana, A.C., da Silva, E.Z., Oliver, C. and Jamur, M.C. 2015. The Role of Mast Cell Specific Chymases and Tryptases in Tumor Angiogenesis Biomed. Res. Int. 1-13.
Derenzini, M. 2003. The AgNORs. Micron 31: 117–120.
Dopson, J.M. and Scase, T.J. 2007. Advances in the diagnosis and management of cutaneous mast cell tumours in dogs. J. Small Anim. Pract. 48: 424-431.
Dorn, C.R., Taylor, D.O., Schneider, R., Hibbard, H.H. and Klauber, M.R. 1968. Survey of animal neoplasms in Alameda and Contra Costa counties, California II. Cancer morbidity in dogs and cats from Alameda Country. J. of the National Cancer Institute 40: 307-318.
Dos Santos Costa Poggiani, S., Terra, E.M., Neto, R.T., Costa, M.T. and Amorim, R.F. 2012. Canine Cutaneous Mast Cell Tumor: Biologic Behavior and Its Correlation with Prognostic Indicators. Open J. Vet. Med. 2: 255-261.
Downing, S. Chien, M.B., Kass, P.H., Moore, P.E. and London, C.A. 2002. Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. Am. J. Vet. Res. 63: 1718–1723.
Duncan, J.R. and Prasse, K.W. 1979. Cytology of canine cutaneous round cell tumors. Vet. Pathol. 16: 673-679.
Epstein, J.B., Scully, C. and Spinelli, J. 1992. Toluidine blue and Lugol's iodine application in the assessment of oral malignant disease and lesions at risk of malignancy. J Oral Pathol Med. 21:160–163.
Fernandez, N.J., West, K.H., Jackson, M.L. and Kidney, B.A. 2005. Immunohistochemical and histochemical stains for differentiating canine cutaneous round cell tumors. Vet. Pathol. 42: 437–445.
Furitsu, T., Tsujimura, T. and Tono, T. 1993. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J. Clin. Invest. 92: 1736–1744.
Galli, S.J., Zsebo, K.M. and Geissler, E.N. 1994. The kit-ligand, stem-cell factor. Adv. in Immunol. 55:1-96.
Gleixner, K.V., Rebuzzi, L., Mayerhofer, M., Gruze, A., Hadzijusufivic, E., Sonneck, K., Vales, A., Kneidinger, M., Samorapoomichit, P., Thaiwong, T., Pickl, W.F., Yuzbasiyan-Gurkan, V., Sillaber, C., Willmann, M. and Valent, P. 2007. Synergistic antiproliferative effects of KIT tyrosine kinase inhibitors on neoplastic canine mast cells. Exp. Hematol. 35: 1510–1521.
Goldschmidt, M.H. and Shofer, F.S. 1992. Skin tumours of the cat and dog. Pergamon press. Oxford, NY, USA. 316p.
Howard, E.B., Sawa, T.R., Nielsen, S.W. and Kenyon, A.J. 1969. Mastocytoma and gastroduodenal ulceration. Pathol. Vet. 6:146-158.
Huntley, JF. 1992. Mast cells and basophils: a review of their heterogeneity and function. J.Comp. Pathol. 107(4): 349-372.
Jackson, D. 1994. The cytology of the contagious (venereal) tumor of dog. Onderstepoort J. Vet. Res. 20:433-442.
Jones, C.L., Grahn, R.A., Chien, M.B., Lyons, L.A. and London, C.A. 2004. Detection of c-kit mutations in canine mast cell tumors using fluorescent poly acrylamide gel electrophoresis. J. Vet. Diagn. Invest. 16: 95–100.
Kitamura, Y. and Fujita, J. 1989. Regulation of mast cell differentiation. Bioessays 10: 193–196.
Kiupel, M., Webster, J.D., Bailey, K.L., Best, S., DeLay, J., Detrisac, C.J., Fitzgerald, S.D., Gamble, D., Ginn, P.E., Goldschmidt,, M.H., Hendrick, M.J., Howerth, E.W., Janovitz, E.B., Langohr, I., Lenz, S.D., Lipscomb, T.P., Miller, M.A., Misdorp, W., Moroff, S., Mullaney, T.P., Neyens, I., O’Toole, D., Ramos-Vara, J., Scase, T.J., Schulman, F.Y., Sledge, D., Smedley, R.C., Smith, K., Snyder, P.W., Southorn, E., Stedman, N.L., Steficek, B.A., Stromberg, P.C., Valli, V.E., Weisbrode, S.E., Yager, J., Heller, J. and Miller, R. 2011. Proposal of a Two-Tier Histologic Grading Sys- tem for Canine Cutaneous Mast Cell Tumors to More Accurately Predict Biological Behavior. Vet. Pathol. 48(1) 147-155.
Kiupel, M., Webster, J.D., Kaneene, J.B., Miller, R. and Yuzbasiyan-Gurkan, V. 2004. The use of KITand tryptase expression patterns as prognostic tools for canine cutaneous mast cell tumors. Vet. Pathol. 41: 371–377.
Kiupel, M., Webster, J.D., Miller, R.A. and Kaneene, J.B. 2005. Impact of tumour depth, tumour location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumours. J. Vet. Med. A. 52: 280-286.
Kube, P., Audige, L., Kuther, K. and Welle, M. 1998. Distribution, Density and Heterogeneity of Canine Mast Cells and Influence of Fixation Techniques Histochem. Cell Biol. 110 (2): 129-135.
Kurz, H. and Wittekind, D. 2001. A new panoptic stain for developmental biology - The mouse placenta paradigm. Annual of Anat. 183: 437-441.
Leclere, M., Desnoyers, M., Beauchamp, G. and Lavoie, J.P. 2006. Comparison of Four Staining Methods for Detection of Mast Cells in Equine Bronchoalveolar Lavage Fluid. J. Vet. Intern. Med. 20:377–381.
Leder, L.D. 1979. The chloroacetate esterase reaction. A usefulmeans of histological diagnosis of hematological disorders from paraffin sections of the skin. Anim. J. Dermatopathol. 1:39-42.
Linnekin, D., DeBerry, C.S and Mou, S. 1997. Lyn associates with the Juxtamembrane region of c-Kit and is activated by stem cell factor in haemopoietic cell and normal progenitor cells. J. Biol. Chem. 272: 27450-27455.
London, C.A., Kisseberth, W.C., Galli, S.J., Geissler, E.N. and Helfand, S.C. 1996 Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine MCTs. J. Comp. Pathol. 115: 399-414.
London, C.A. and Segun, B. 2003. Mast cell tumors in the dog. Vet Clin. North Am. Small An. Pract. 33: 473-489.
Metcalfe, D.D., Baram, D. and Mekori, Y.A. 1997. Mast cells. Physiol. Rev. 77: 1033-1079.
Misdrop, W. 2004. Mast cells and canine mast cell tumuors. A review Vet. Q. 26:156-169.
Morini, M., Bettini, G., Preziosi, R. and Mandrioli, L. 2004. C-kit gene product (CD117) immunoreactivity in canine and feline paraffin sections. J. Histochem. Cytochem. 52: 705–708.
Nocka, K., Buck, J., Levi, E. and Besmer, P. 1990. Candidate ligand for the c-kit transmembrane kinaseb receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors Embo. J. 9: 3287-3294.
Northrup, N.C., Howerth, E.W., Harmon, B.G., Brown, C.A., Carmicheal, K.P., Garcia, A.P., Latimer, K.S., Munday, J.S., Rakich, P.M., Richey, L.J., Stedman, N.L. and Gieger, T.L. 2005. Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference. J. Vet. Diagn. Invest. 17: 561-564.
Ogura, S., Abe, S., Sukoh, N, Kunikane, H., Nakajima, I., Inoue, K. and Kawakami, Y. 1992. Correlation between nucleolar organizer regions visualized by silver staining and the growth rate in lung adenocarcinoma. Cancer 70: 63–68.
O’Keefe, D.A. 1990. Canine mast cell tumors. Vet. Clin. N. Am.-Small 20:1105-1115.
Pakhrin, B., Kang, M.S., Bae, I.H., Park, M.S., You, M.H., Kim, J.H., Yoon, B.I., Choi, Y.K. and Kim, D.Y. 2007. Retrospective study of canine cutaneous tumors in Korea. J. Vet. Sci. 8(3): 229-236.
Patnaik, A.K., Ehler, W.J. and Macwem, E.G. 1984. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet. Pathol. 21: 469-474.
Preziosi, R., Sarli, G. and Paltrinieri, M. 2004. Prognostic value of intratumoral vessel density in cutaneous mast cell tumours of the dog. J. Comp Pathol. 130(2-3): 143-151.
Prussin, C. and Metcalfe, D.D. 2003. IgE, mast cells, basophils, and eosinophils. J. Allergy Clin. Immunol. 111(2 Suppl): 486-494.
Riva, F., Brizzola, S., Stefanello, D., Crema, S. and Turin, L. 2005. A study of mutations in the c-kit gene of 32 dogs with mastocytoma. J. Vet. Diagn. Invest. 17: 385–388.
Roels, S., Tilmant, K. and Ducatelle, R. 1999. PCNA and Ki67 proliferation markers as criteria for prediction of clinical behaviour of melanocytic tumours in cats and dogs. J. Comp. Patholo. 121: 13–24.
Scase, T.J., Edwards, D., Miller, J. Henley, W., Smith, K., Blunden, A. and Murphy, S. 2006. Canine mast cell tumors: correlation of apoptosis and proliferation markers with prognosis. J. Vet. Intern Med. 20: 151-158.
Serve, H., Yee, N.S., Stella, G., Sepplorenzino, L., Tan, J.C. and Besmer, P. 1995. Differential roles of PI3-Kinase and KIT tyrosine-821 in KIT receptor-mediated proliferation, survival and cell adhesion in mast cells. Embo. J. 14: 473-483.
Simoes, J.P. and Schoning, P. 1994. Canine mast cell tumors: a comparison of staining techniques. J. Vet. Diagn. Invest. 6: 458-465.
Simoes, J.P., Schoning, P. and Butine, M. 1994. Prognosis of canine mast cell tumors: a comparison of three methods. Vet. Pathol. 31: 637-647.
Strefezzi, R.F., Kleeb, S.R., Xavier, J.G. and Catão-Dias J.L. 2009. Prognostic indicators for mast cell tumors. Braz. J. Vet. Pathol. 2(2): 110-121.
Strefezzi, R.F.S., Xavier, J.G. and Catao-Dias, J.L. 2003. Morphometry of canine cutaneous mast cell tumors. Vet. Pathol. 40: 268-275.
Trere, D., Pession, A., Montanaro, L., Chieco, P. and Derenzini, M. 1997. AgNOR protein expression and tumor growth rate of human carcinoma xenografts growing subcutaneously in nude mice. European J. Histochem. 41(2): 153–154.
Walls, A.F., Jones, D.B., Williams, J.H., Church, M.K. and Holgate, S.T. 1990. Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. J Pathol. 162: 119-126.
Webster, J.D., Kiupel, M., Kaneene, J.B., Miller, R. and Yuzbasiyan-Gurkan, V. 2004. The Use of KIT and tryptase epression patterns as prognostic tools for canine cutaneous mast cell tumors, Vet. Pathol. 41(3): 371-377.
Webster, J.D., Kiupel, M. and Yuzbasiyan-Gurkan, V. 2006a. Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors. BMC Cancer 6: 85.
Webster, J.D., Yuzbasiyan-Gurkan, V., Kaneene, J.B., Miller, R., Resau, J.H. and Kiupel, M. 2006b. The role of c-KIT in tumorigenesis: evaluation in canine cutaneous mast cell tumors. Neoplasia 8: 104–111.
Webster, J.D., Yuzbasiyan-Gurkan, V., Miller, R.A., Kaneene, J.B. and Kiupel, M. 2007. Cellular proliferation in canine cutaneous mast cell tumors: associations with c-KIT and its role in prognostication. Vet. Pathol. 44: 298–308.
Welle, M.M., Rohrer, B.C, Howard, J. and Rufenacht, S. 2008. Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment. Vet. Dermatol. 19: 321-339.
Zemke, D., Yamini, B. and Yuzbasiyan-Gurkan, V. 2002. Mutations in the juxtamembrane domain of c-KIT are associated with higher grade mast cell tumors in dogs. Vet. Pathol. 39: 529–35.
Bancroft, J. and Gamble, M. 2008. Theory and Practice of Histological Techniques. 6th ed. Churchill Livingstone/Elsevier, Philadelphia. 725 p.
Beaven, M.A. and Metzger, H. 1993. Signal transduction by Fc receptors: the Fc epsilon RI case. Immunol. Today 14(5): 222-226.
De Souza Junior, D.A., Santana, A.C., da Silva, E.Z., Oliver, C. and Jamur, M.C. 2015. The Role of Mast Cell Specific Chymases and Tryptases in Tumor Angiogenesis Biomed. Res. Int. 1-13.
Derenzini, M. 2003. The AgNORs. Micron 31: 117–120.
Dopson, J.M. and Scase, T.J. 2007. Advances in the diagnosis and management of cutaneous mast cell tumours in dogs. J. Small Anim. Pract. 48: 424-431.
Dorn, C.R., Taylor, D.O., Schneider, R., Hibbard, H.H. and Klauber, M.R. 1968. Survey of animal neoplasms in Alameda and Contra Costa counties, California II. Cancer morbidity in dogs and cats from Alameda Country. J. of the National Cancer Institute 40: 307-318.
Dos Santos Costa Poggiani, S., Terra, E.M., Neto, R.T., Costa, M.T. and Amorim, R.F. 2012. Canine Cutaneous Mast Cell Tumor: Biologic Behavior and Its Correlation with Prognostic Indicators. Open J. Vet. Med. 2: 255-261.
Downing, S. Chien, M.B., Kass, P.H., Moore, P.E. and London, C.A. 2002. Prevalence and importance of internal tandem duplications in exons 11 and 12 of c-kit in mast cell tumors of dogs. Am. J. Vet. Res. 63: 1718–1723.
Duncan, J.R. and Prasse, K.W. 1979. Cytology of canine cutaneous round cell tumors. Vet. Pathol. 16: 673-679.
Epstein, J.B., Scully, C. and Spinelli, J. 1992. Toluidine blue and Lugol's iodine application in the assessment of oral malignant disease and lesions at risk of malignancy. J Oral Pathol Med. 21:160–163.
Fernandez, N.J., West, K.H., Jackson, M.L. and Kidney, B.A. 2005. Immunohistochemical and histochemical stains for differentiating canine cutaneous round cell tumors. Vet. Pathol. 42: 437–445.
Furitsu, T., Tsujimura, T. and Tono, T. 1993. Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. J. Clin. Invest. 92: 1736–1744.
Galli, S.J., Zsebo, K.M. and Geissler, E.N. 1994. The kit-ligand, stem-cell factor. Adv. in Immunol. 55:1-96.
Gleixner, K.V., Rebuzzi, L., Mayerhofer, M., Gruze, A., Hadzijusufivic, E., Sonneck, K., Vales, A., Kneidinger, M., Samorapoomichit, P., Thaiwong, T., Pickl, W.F., Yuzbasiyan-Gurkan, V., Sillaber, C., Willmann, M. and Valent, P. 2007. Synergistic antiproliferative effects of KIT tyrosine kinase inhibitors on neoplastic canine mast cells. Exp. Hematol. 35: 1510–1521.
Goldschmidt, M.H. and Shofer, F.S. 1992. Skin tumours of the cat and dog. Pergamon press. Oxford, NY, USA. 316p.
Howard, E.B., Sawa, T.R., Nielsen, S.W. and Kenyon, A.J. 1969. Mastocytoma and gastroduodenal ulceration. Pathol. Vet. 6:146-158.
Huntley, JF. 1992. Mast cells and basophils: a review of their heterogeneity and function. J.Comp. Pathol. 107(4): 349-372.
Jackson, D. 1994. The cytology of the contagious (venereal) tumor of dog. Onderstepoort J. Vet. Res. 20:433-442.
Jones, C.L., Grahn, R.A., Chien, M.B., Lyons, L.A. and London, C.A. 2004. Detection of c-kit mutations in canine mast cell tumors using fluorescent poly acrylamide gel electrophoresis. J. Vet. Diagn. Invest. 16: 95–100.
Kitamura, Y. and Fujita, J. 1989. Regulation of mast cell differentiation. Bioessays 10: 193–196.
Kiupel, M., Webster, J.D., Bailey, K.L., Best, S., DeLay, J., Detrisac, C.J., Fitzgerald, S.D., Gamble, D., Ginn, P.E., Goldschmidt,, M.H., Hendrick, M.J., Howerth, E.W., Janovitz, E.B., Langohr, I., Lenz, S.D., Lipscomb, T.P., Miller, M.A., Misdorp, W., Moroff, S., Mullaney, T.P., Neyens, I., O’Toole, D., Ramos-Vara, J., Scase, T.J., Schulman, F.Y., Sledge, D., Smedley, R.C., Smith, K., Snyder, P.W., Southorn, E., Stedman, N.L., Steficek, B.A., Stromberg, P.C., Valli, V.E., Weisbrode, S.E., Yager, J., Heller, J. and Miller, R. 2011. Proposal of a Two-Tier Histologic Grading Sys- tem for Canine Cutaneous Mast Cell Tumors to More Accurately Predict Biological Behavior. Vet. Pathol. 48(1) 147-155.
Kiupel, M., Webster, J.D., Kaneene, J.B., Miller, R. and Yuzbasiyan-Gurkan, V. 2004. The use of KITand tryptase expression patterns as prognostic tools for canine cutaneous mast cell tumors. Vet. Pathol. 41: 371–377.
Kiupel, M., Webster, J.D., Miller, R.A. and Kaneene, J.B. 2005. Impact of tumour depth, tumour location and multiple synchronous masses on the prognosis of canine cutaneous mast cell tumours. J. Vet. Med. A. 52: 280-286.
Kube, P., Audige, L., Kuther, K. and Welle, M. 1998. Distribution, Density and Heterogeneity of Canine Mast Cells and Influence of Fixation Techniques Histochem. Cell Biol. 110 (2): 129-135.
Kurz, H. and Wittekind, D. 2001. A new panoptic stain for developmental biology - The mouse placenta paradigm. Annual of Anat. 183: 437-441.
Leclere, M., Desnoyers, M., Beauchamp, G. and Lavoie, J.P. 2006. Comparison of Four Staining Methods for Detection of Mast Cells in Equine Bronchoalveolar Lavage Fluid. J. Vet. Intern. Med. 20:377–381.
Leder, L.D. 1979. The chloroacetate esterase reaction. A usefulmeans of histological diagnosis of hematological disorders from paraffin sections of the skin. Anim. J. Dermatopathol. 1:39-42.
Linnekin, D., DeBerry, C.S and Mou, S. 1997. Lyn associates with the Juxtamembrane region of c-Kit and is activated by stem cell factor in haemopoietic cell and normal progenitor cells. J. Biol. Chem. 272: 27450-27455.
London, C.A., Kisseberth, W.C., Galli, S.J., Geissler, E.N. and Helfand, S.C. 1996 Expression of stem cell factor receptor (c-kit) by the malignant mast cells from spontaneous canine MCTs. J. Comp. Pathol. 115: 399-414.
London, C.A. and Segun, B. 2003. Mast cell tumors in the dog. Vet Clin. North Am. Small An. Pract. 33: 473-489.
Metcalfe, D.D., Baram, D. and Mekori, Y.A. 1997. Mast cells. Physiol. Rev. 77: 1033-1079.
Misdrop, W. 2004. Mast cells and canine mast cell tumuors. A review Vet. Q. 26:156-169.
Morini, M., Bettini, G., Preziosi, R. and Mandrioli, L. 2004. C-kit gene product (CD117) immunoreactivity in canine and feline paraffin sections. J. Histochem. Cytochem. 52: 705–708.
Nocka, K., Buck, J., Levi, E. and Besmer, P. 1990. Candidate ligand for the c-kit transmembrane kinaseb receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors Embo. J. 9: 3287-3294.
Northrup, N.C., Howerth, E.W., Harmon, B.G., Brown, C.A., Carmicheal, K.P., Garcia, A.P., Latimer, K.S., Munday, J.S., Rakich, P.M., Richey, L.J., Stedman, N.L. and Gieger, T.L. 2005. Variation among pathologists in the histologic grading of canine cutaneous mast cell tumors with uniform use of a single grading reference. J. Vet. Diagn. Invest. 17: 561-564.
Ogura, S., Abe, S., Sukoh, N, Kunikane, H., Nakajima, I., Inoue, K. and Kawakami, Y. 1992. Correlation between nucleolar organizer regions visualized by silver staining and the growth rate in lung adenocarcinoma. Cancer 70: 63–68.
O’Keefe, D.A. 1990. Canine mast cell tumors. Vet. Clin. N. Am.-Small 20:1105-1115.
Pakhrin, B., Kang, M.S., Bae, I.H., Park, M.S., You, M.H., Kim, J.H., Yoon, B.I., Choi, Y.K. and Kim, D.Y. 2007. Retrospective study of canine cutaneous tumors in Korea. J. Vet. Sci. 8(3): 229-236.
Patnaik, A.K., Ehler, W.J. and Macwem, E.G. 1984. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Vet. Pathol. 21: 469-474.
Preziosi, R., Sarli, G. and Paltrinieri, M. 2004. Prognostic value of intratumoral vessel density in cutaneous mast cell tumours of the dog. J. Comp Pathol. 130(2-3): 143-151.
Prussin, C. and Metcalfe, D.D. 2003. IgE, mast cells, basophils, and eosinophils. J. Allergy Clin. Immunol. 111(2 Suppl): 486-494.
Riva, F., Brizzola, S., Stefanello, D., Crema, S. and Turin, L. 2005. A study of mutations in the c-kit gene of 32 dogs with mastocytoma. J. Vet. Diagn. Invest. 17: 385–388.
Roels, S., Tilmant, K. and Ducatelle, R. 1999. PCNA and Ki67 proliferation markers as criteria for prediction of clinical behaviour of melanocytic tumours in cats and dogs. J. Comp. Patholo. 121: 13–24.
Scase, T.J., Edwards, D., Miller, J. Henley, W., Smith, K., Blunden, A. and Murphy, S. 2006. Canine mast cell tumors: correlation of apoptosis and proliferation markers with prognosis. J. Vet. Intern Med. 20: 151-158.
Serve, H., Yee, N.S., Stella, G., Sepplorenzino, L., Tan, J.C. and Besmer, P. 1995. Differential roles of PI3-Kinase and KIT tyrosine-821 in KIT receptor-mediated proliferation, survival and cell adhesion in mast cells. Embo. J. 14: 473-483.
Simoes, J.P. and Schoning, P. 1994. Canine mast cell tumors: a comparison of staining techniques. J. Vet. Diagn. Invest. 6: 458-465.
Simoes, J.P., Schoning, P. and Butine, M. 1994. Prognosis of canine mast cell tumors: a comparison of three methods. Vet. Pathol. 31: 637-647.
Strefezzi, R.F., Kleeb, S.R., Xavier, J.G. and Catão-Dias J.L. 2009. Prognostic indicators for mast cell tumors. Braz. J. Vet. Pathol. 2(2): 110-121.
Strefezzi, R.F.S., Xavier, J.G. and Catao-Dias, J.L. 2003. Morphometry of canine cutaneous mast cell tumors. Vet. Pathol. 40: 268-275.
Trere, D., Pession, A., Montanaro, L., Chieco, P. and Derenzini, M. 1997. AgNOR protein expression and tumor growth rate of human carcinoma xenografts growing subcutaneously in nude mice. European J. Histochem. 41(2): 153–154.
Walls, A.F., Jones, D.B., Williams, J.H., Church, M.K. and Holgate, S.T. 1990. Immunohistochemical identification of mast cells in formaldehyde-fixed tissue using monoclonal antibodies specific for tryptase. J Pathol. 162: 119-126.
Webster, J.D., Kiupel, M., Kaneene, J.B., Miller, R. and Yuzbasiyan-Gurkan, V. 2004. The Use of KIT and tryptase epression patterns as prognostic tools for canine cutaneous mast cell tumors, Vet. Pathol. 41(3): 371-377.
Webster, J.D., Kiupel, M. and Yuzbasiyan-Gurkan, V. 2006a. Evaluation of the kinase domain of c-KIT in canine cutaneous mast cell tumors. BMC Cancer 6: 85.
Webster, J.D., Yuzbasiyan-Gurkan, V., Kaneene, J.B., Miller, R., Resau, J.H. and Kiupel, M. 2006b. The role of c-KIT in tumorigenesis: evaluation in canine cutaneous mast cell tumors. Neoplasia 8: 104–111.
Webster, J.D., Yuzbasiyan-Gurkan, V., Miller, R.A., Kaneene, J.B. and Kiupel, M. 2007. Cellular proliferation in canine cutaneous mast cell tumors: associations with c-KIT and its role in prognostication. Vet. Pathol. 44: 298–308.
Welle, M.M., Rohrer, B.C, Howard, J. and Rufenacht, S. 2008. Canine mast cell tumours: a review of the pathogenesis, clinical features, pathology and treatment. Vet. Dermatol. 19: 321-339.
Zemke, D., Yamini, B. and Yuzbasiyan-Gurkan, V. 2002. Mutations in the juxtamembrane domain of c-KIT are associated with higher grade mast cell tumors in dogs. Vet. Pathol. 39: 529–35.