Kit Receptor Expression in Canine Cutaneous Mast Cell Tumors (CMCTs) Without C-Kit Mutation

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Abstract

Histopathological examination, grading, immunohistochemical staining and molecular genetic examinations are the proposed criteria that should be used for cutaneous mast cell tumors (CMCTs) classification. The presence of aberrant CD117 expression and mutations of the c-kit proto-oncogene could be an indicative parameter for final histological grading. Determination of the connection between the localization of KIT receptor expression and the histological grade of CMCTs without c-kit proto-oncogene mutations was the main goal of this study. The study included twenty four CMCTs and six control skin samples from 30 dogs of different ages, breed and sex. Formalinfixed and paraffin-embedded tissue samples were stained with hematoxylin-eosin and toluidine blue and immunohistochemically tested for CD117 expression. DNA was extracted from the same paraffin blocks and subsequent polymerase chain reaction amplification was performed using PE1 and PE2 primers. Degree of malignancy was determined based on the presence of mitotic figures, multinucleated cells, bizarre nuclei and karyomegaly in 10 high power fields. Based on histological features, fourteen of 24 CMCTs were of a high histological grade, while ten were classified as a lowgrade malignancy. CD117 cytoplasmic expression was observed in nine of fourteen high-grade malignancy CMCTs, which confirms the link between the aberrant CD117 expression and increased cell proliferation.

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  • 1. Welle MM Bley CR Howard J Rufenacht S: Canine mast cell tumours: a review of the pathogenesis clinical features pathology and treatment. Veterinary dermatology 2008 19(6):321-339.

  • 2. Feghiu A Crînganu D Dumitrescu F Pascal M Vasilescu F Militaru M: Nasal transmissible venereal tumor in a jack russel terrier bitch. Acta Veterinaria - Beograd 2015 65(1):143-148.

  • 3. Aleksić-Kovačević S Kukolj V Jelesijević T Jovanović M: Retrospective analysis of canine mesenchymal tumors of skin and soft tissues. Acta Veterinaria - Beograd 2005 55(5-6):521-529.

  • 4. Strefezz i R Xavier J Kleeb S Catão-Dias J: Prognostic indicators for mast cell tumors. Brazilian Journal of Veterinary Pathology 2009 2(2):110-121.

  • 5. Madewell BR Munn RJ Phillips LK: Ultrastructure of canine feline and bovine mast cell neoplasms. American journal of veterinary research 1984 45(10):2066-2073.

  • 6. Riva F B rizzola S Stefanello D Crema S Turin L: A study of mutations in the c-kit gene of 32 dogs with mastocytoma. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians Inc 2005 17(4):385-388.

  • 7. Jones CL Grahn RA Chien MB Lyons LA London CA: Detection of c-kit mutations in canine mast cell tumors using fluorescent polyacrylamide gel electrophoresis. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians Inc 2004 16(2):95-100.

  • 8. Kiupel M Webster JD Kaneene JB Miller R Yuzbasiyan-Gurkan V: The use of KIT and tryptase expression patterns as prognostic tools for canine cutaneous mast cell tumors. Veterinary pathology 2004 41(4):371-377.

  • 9. Webster J D Yuzbasiyan-Gurkan V Miller RA Kaneene JB Kiupel M: Cellular proliferation in canine cutaneous mast cell tumors: associations with c-KIT and its role in prognostication. Veterinary pathology 2007 44(3):298-308.

  • 10. Patnaik AK Ehler WJ MacEwen EG: Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Veterinary pathology 1984 21(5):469-474.

  • 11. Kiupel M Webster JD Bailey KL Best S DeLay J Detrisac CJ Fitzgerald SD Gamble D Ginn PE Goldschmidt MH et al: Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior. Veterinary pathology 2011 48(1):147-155.

  • 12. Sabattini S Scarpa F Berlato D Bettini G: Histologic grading of canine mast cell tumor: is 2 better than 3? Veterinary pathology 2015 52(1):70-73.

  • 13. Takeuchi Y Fujino Y Watanabe M Takahashi M Nakagawa T Takeuchi A Bonkobara M Kobayashi T Ohno K Uchida K et al: Validation of the prognostic value of histopathological grading or c-kit mutation in canine cutaneous mast cell tumours: A retrospective cohort study. The Veterinary Journal 2013 196(3):492-498.

  • 14. Gil da Costa RM Matos E Rema A Lopes C Pires MA Gartner F: CD117 immunoexpression in canine mast cell tumours: correlations with pathological variables and proliferation markers. BMC veterinary research 2007 3:19.

  • 15. Thompson J: Canine Mast Cell Tumors: Characterization of Subcutaneous Tumors and Receptor Tyrosine Kinase Profiling. The University of Guelph; 2012.

  • 16. Reguera MJ Rabanal RM Puigdemont A Ferrer L: Canine mast cell tumors express stem cell factor receptor. The American Journal of dermatopathology 2000 22(1):49-54.

  • 17. Preziosi R Morini M Sarli G: Expression of the KIT protein (CD117) in primary cutaneous mast cell tumors of the dog. Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians Inc 2004 16(6):554-561.

  • 18. Webster JD Yuzbasiyan-Gurkan V Kaneene JB Miller R Resau JH Kiupel M: The role of c-KIT in tumorigenesis: evaluation in canine cutaneous mast cell tumors. Neoplasia 2006 8(2):104-111.

  • 19. Aleksić- Kovačević S Kukolj J Jelesijević T Jovanović M: Retrospective analysis of canine mesenchymal tumors of skin and soft tissues. Acta Veterinaria 2005 55(5-6):521-529.

  • 20. Stevanović R Vu čićević I Marinković D Aleksić-Kovačević S: Morphology gradation and frequency of mastocytoma in dogs. Veterinarski glasnik 2013 67(3-4):153-162.

  • 21. Romansik EM Reilly CM Kass PH Moore PF London CA: Mitotic index is predictive for survival for canine cutaneous mast cell tumors. Veterinary pathology 2007 44(3):335-341.

  • 22. Marinković D Milčić-Matić N Jovanović M Vučićević I Nešić S Aničič M Aleksić- Kovačević S: Morphological features and kit receptor expression in canine cutaneous mast cell tumor and systemic mastocytosis. Acta Veterinaria 2015 65(2):226-237.

  • 23. Sailasuta A Ketpun D Piyaviriyakul P Theerawata nasirikul S Theewasutrakul P Rungsipipat A: The Relevance of CD117-Immunocytochemistry Staining Patterns to Mutational Exon-11 in c-kit Detected by PCR from Fine-Needle Aspirated Canine Mast Cell Tumor Cells. Veterinary medicine international 2014 2014:787498.

  • 24. Zemke D Yamini B Yuzbasiyan-Gurkan V: Mutations in the juxtamembrane domain of c-KIT are associated with higher grade mast cell tumors in dogs. Veterinary pathology 2002 39(5):529-535.

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