Immunohistochemical Expression of Receptor Tyrosine Kinase (RTK) in Canine Brain Tumors

다국어 초록 (Multilingual Abstract)

Receptor tyrosine kinases (RTK) are major promising targets in anticancer therapy in human and veterinary medicine. Using immunohistochemistry method, we evaluated the expressionof five types RTK (PDGFR-α, PDGFR-β, VEGFR 2, c-Kit and Abl) in the six canine brain tumor samples (2 meningioma, 2 astrocytoma, 1 ependymoma and 1 choroid plexus papilloma). A total of five samples expressed PDGFR-β (5/6), one sample, the choroid plexus papilloma, expressed c-Kit (1/6), and a total of two samples expressed Abl (2/6). None of the samples showed expression of PDGFR-α and VEGFR 2. We demonstrate that a significant portion of canine brain tumors express tyrosine receptors for growth factors and show that these receptors generally localize to tumor cell membranes and the cytoplasm.
Evaluation of immunohistochemical expression for the RTKs PDGFR-β, c-Kit, and Alb in canine brain samples reveals an interesting potential for molecular targeting by TKIs in therapeutic studies of canine brain tumors, and more studies will be needed to assess the interactions and efficacy of these RTKs and TKIs. Based on these results, we have some evidence for novel chemotherapeutic trials using TKIs for canine nervous tumors.

참고문헌 (Reference)

1 Ma PC, "c-Met : structure, functions and potential for therapeutic inhibition" 22 : 309-325, 2003

2 Pfister C, "Vascular endothelial growth factor signals through platelet-derived growth factor receptor beta in meningiomas in vitro" 107 : 1702-1713, 2012

3 Dickinson PJ, "Vascular endothelial growth factor mRNA expression and peritumoral edema in canine primary central nervous system tumors" 45 : 131-139, 2008

4 Platt SR, "Vascular endothelial growth factor expression in canine intracranial meningiomas and association with patient survival" 20 : 663-668, 2006

5 London CA, "Tyrosine kinase inhibitors in veterinary medicine" 24 : 106-112, 2009

6 Liang ML, "Tyrosine kinase expression in pediatric high grade astrocytoma" 87 : 247-253, 2008

7 Folkman J, "Tumor angiogenesis" 43 : 175-203, 1985

8 Graham JC, "The prognostic significance of angiogenesis in canine mammary tumors" 13 : 416-418, 1999

9 Wanebo HJ, "Targeting growth factors and angiogenesis; using small molecules in malignancy" 25 : 279-292, 2006

10 Balana C, "Sunitinib administered prior to radiotherapy in patients with non-resectable glioblastoma : results of a phase II study" 9 : 321-329, 2014

11 Higgins RJ, "Spontaneous canine gliomas : overexpression of EGFR, PDGFRalpha and IGFBP2 demonstrated by tissue microarray immunophenotyping" 98 : 49-55, 2010

12 Fletcher JA, "Role of KIT and platelet-derived growth factor receptors as oncoproteins" 31 : 4-11, 2004

13 Shchemelinin I, "Protein kinases, their function and implication in cancer and other diseases" 52 : 81-100, 2006

14 Shchemelinin I, "Protein kinase inhibitors" 52 : 137-148, 2006

15 Wergin MC, "Preliminary study of plasma vascular endothelial growth factor(VEGF)during low-and high-dose radiation therapy of dogs with spontaneous tumors" 45 : 247-254, 2004

16 Nupponen NN, "Plateletderived growth factor receptor expression and amplification in choroid plexus carcinomas" 21 : 265-270, 2008

17 Figarella-Branger D, "Platelet-derived growth factor(PDGF)and receptor(PDGFR)expression in human meningiomas : correlations with clinicopathological features and cytogenetic analysis" 20 : 439-447, 1994

18 Stoica G, "Morphology, immunohistochemistry, and genetic alterations in dog astrocytomas" 41 : 10-19, 2004

19 Gomes AL, "Molecular alterations of KIT oncogene in gliomas" 29 : 399-408, 2007

20 Wakeling AE, "Inhibitors of growth factor signalling" 12 (12): S183-S187, 2005

21 Ide T, "Immunohistochemical characterization of canine neuroepithelial tumors" 47 : 741-750, 2010

22 Haberler C, "Immunohistochemical analysis of plateletderived growth factor receptor-alpha, -beta, c-kit, c-abl, and arg proteins in glioblastoma : possible implications for patient selection for imatinib mesylate therapy" 76 : 105-109, 2006

23 Horak P, "Imatinib mesylate treatment of recurrent meningiomas in preselected patients : a retrospective analysis" 109 : 323-330, 2012

24 Dresemann G, "Imatinib and hydroxyurea in pretreated progressive glioblastoma multiforme : a patient series" 16 : 1702-1708, 2005

25 Lipsitz D, "Glioblastoma multiforme : clinical findings, magnetic resonance imaging, and pathology in five dogs" 40 : 659-669, 2003

26 Rossmeisl JH, "Expression of vascular endothelial growth factor in tumors and plasma from dogs with primary intracranial neoplasms" 68 : 1239-1245, 2007

27 Berkman RA, "Expression of the vascular permeability factor/vascular endothelial growth factor gene in central nervous system neoplasms" 91 : 153-159, 1993

28 Dickinson PJ, "Expression of receptor tyrosine kinases VEGFR-1(FLT-1), VEGFR-2(KDR), EGFR-1, PDGFRalpha and c-Met in canine primary brain tumours" 4 : 132-140, 2006

29 Kuratsu JI, "Expression of PDGF, PDGF-receptor, EGF-receptor and sex hormone receptors on meningioma" 131 : 289-293, 1994

30 Yang SY, "Expression of PDGF and its receptor as well as their relationship to proliferating activity and apoptosis of meningiomas in human meningiomas" 8 (8): 49-53, 2001

31 Koleske AJ, "Essential roles for the Abl and Arg tyrosine kinases in neurulation" 21 : 1259-1272, 1998

32 Shamah SM, "Detection of activated platelet-derived growth factor receptors in human meningioma" 57 : 4141-4147, 1997

33 Van Etten RA, "Cycling, stressed-out and nervous : cellular functions of c-Abl" 9 : 179-186, 1999

34 Kinsella P, "Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib" 318 : 641-652, 2012

35 Cetin N, "CD117 expression in glial tumors" 75 : 195-202, 2005

36 Harrigan MR, "Angiogenic factors in the central nervous system" 53 : 639-660, 2003

37 Virag J, "Angiogenesis and angiogenic tyrosine kinase receptor expression in pediatric brain tumors" 20 : 417-426, 2014

38 Nobusawa S, "Amplification of the PDGFRA, KIT and KDR genes in glioblastoma : a population-based study" 31 : 583-588, 2011