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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Epidermal Growth Factor Receptor and Ki-67 Expression in Canine Gliomas
A R Fraser1, B Bacci2, M A le Chevoir3
1Translational Research and Animal Clinical Trial Studies Group, Section of Veterinary Neurology and Neurosurgery, Faculty of Veterinary and Agricultural Science, The University of Melbourne, Victoria, Australia Anderson Moores Veterinary Specialists, The Granary, Bunstead Barns, Poles Lane, Hursley, Winchester, Hampshire, United Kingdom anne.fraser@andersonmoores.com.
Abstract:
Novel therapies, including molecular targeted therapies, are being developed for the treatment of human gliomas. To use such therapies for canine gliomas, more complete characterization of molecular targets is required. Epidermal growth factor receptor (EGFR) is one such therapeutic target used in human glioma trials, and the Ki-67 labeling index (LI) is a marker of proliferation and a prognostic indicator. The objectives of this cross-sectional study were to evaluate the expression of EGFR and Ki-67 in canine gliomas and to determine if immunopositivity is associated with tumor type and histologic grade. Thirty-one formalin-fixed, paraffin-embedded canine gliomas were evaluated for EGFR and Ki-67 expression by immunohistochemistry. EGFR immunopositivity was evaluated using a semi-quantitative score and the Ki-67 LI calculated based on the percentage of positive cells. EGFR and Ki-67 expression were identified in 16 of 31 (52%) and 28 of 31 (90%) tumors, respectively. EGFR expression was significantly greater in high-grade tumors compared with low-grade tumors (P = .04) and was significantly greater in gliomatosis cerebri compared with oligodendroglioma (P = .002), astrocytoma (P = .01), and oligoastrocytoma (P = .04). The Ki-67 LI was significantly greater in high-grade tumors compared with low grade tumors (P = .02); the median Ki-67 LI was 2.3% (range, 0%-17.6%) for low-grade tumors and 9.3% (range, 1.7%-41.0%) for high-grade tumors. A significant moderate correlation was identified between EGFR immunopositivity and Ki-67 LI (r = 0.47, P = .007). Overall, EGFR may be a suitable therapeutic target for some canine gliomas, particularly gliomatosis cerebri.
Insights
Epidermal growth factor receptor (EGFR) and Ki-67 are expressed in canine gliomas. EGFR shows higher expression in high-grade tumors and gliomatosis cerebri, suggesting its potential as a therapeutic target.
Area of Science:
- Veterinary Oncology
- Molecular Pathology
- Canine Cancer Research
Background:
- Novel molecular targeted therapies are emerging for human gliomas.
- Characterizing molecular targets in canine gliomas is crucial for adapting human therapies.
- Epidermal growth factor receptor (EGFR) is a key therapeutic target in human glioma research.
Purpose of the Study:
- To evaluate the expression of EGFR and Ki-67 in canine gliomas.
- To determine the association between EGFR and Ki-67 immunopositivity with tumor type and histologic grade.
- To assess the potential of EGFR as a therapeutic target in canine gliomas.
Main Methods:
- Cross-sectional study of 31 formalin-fixed, paraffin-embedded canine gliomas.
- Immunohistochemistry used to assess EGFR and Ki-67 expression.
- EGFR evaluated using semi-quantitative scoring; Ki-67 labeling index (LI) calculated as percentage of positive cells.
Main Results:
- EGFR and Ki-67 expression detected in 52% and 90% of tumors, respectively.
- Significantly higher EGFR expression in high-grade vs. low-grade gliomas (P = .04).
- Significantly higher EGFR expression in gliomatosis cerebri compared to other glioma types (P ≤ .04).
- Ki-67 LI significantly higher in high-grade tumors (median 9.3%) vs. low-grade tumors (median 2.3%) (P = .02).
- Moderate positive correlation between EGFR immunopositivity and Ki-67 LI (r = 0.47, P = .007).
Conclusions:
- EGFR is expressed in canine gliomas, particularly in high-grade tumors and gliomatosis cerebri.
- Ki-67 LI is a reliable indicator of tumor grade in canine gliomas.
- EGFR shows promise as a potential therapeutic target for specific canine gliomas, including gliomatosis cerebri.

