title: Spontaneous canine gliomas: overexpression of EGFR, PDGFRalpha and IGFBP2 demonstrated by tissue microarray immunophenotyping.
abstract: Fifty-seven spontaneous canine gliomas were histologically classified and graded using the latest World Health Organization (WHO 2007) criteria for classification of human gliomas. A total of 19 canine astrocytomas were classified as follows: grade IV (GBM) n = 7; grade III n = 5; and grade II, n = 7. Thirty-eight oligodendrogliomas were classified as either grade III (anaplastic) n = 35 or low grade II n = 3. Tissue microarray (TMA) immunohistochemistry was used to evaluate tumor expression of EGFR, PDGFRa and IGFBP2, three key molecules of known pathophysiological importance in human gliomas. Findings were correlated with tumor classification and grade. Increased EGFR expression was demonstrated in 57% of GBMs, 40% of grade III and 28% of grade II astrocytomas. EGFR expression occurred in only 3% of grade III oligodendrogliomas. Increased expression of PDGFRalpha was demonstrated in 43% of GBMs, 20% of grade III, and 14% of grade II astrocytomas. In the oligodendroglioma series, 94% of grade III tumors overexpressed PDGFRalpha. IGFBP2 expression was detected in 71, 60 and 28% of GBMs, grade III and grade II astrocytomas respectively. IGFBP2 expression occurred in 48% of anaplastic and in 33% of low grade oligodendrogliomas. Expression of EGFR, PDGFRalpha or IGFBP2 was not detected in normal canine CNS control TMA cores. The incidence of overexpression of EGFR, PDGFRalpha and IGFBP2 in these canine gliomas closely parallels that in human tumors of similar type and grade. These findings support a role for the spontaneous canine glioma model in directed pathway-targeting therapeutic studies.
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA. rjhiggins@ucdavis.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Higgins
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Dickinson
authors.forename: Richard A
authors.initials: RA
authors.lastname: LeCouteur
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bollen
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Corely
authors.forename: Lynnette M
authors.initials: LM
authors.lastname: Moore
authors.forename: Wei
authors.initials: W
authors.lastname: Zang
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology / Q000662:veterinary*; D004285:Dogs; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005910:Glioma / Q000145:classification / Q000378:metabolism* / Q000473:pathology / Q000662:veterinary*; D016130:Immunophenotyping / Q000379:methods*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D066246:ErbB Receptors; D020796:Receptor, Platelet-Derived Growth Factor alpha