Expression of Oligodendrocyte Precursor Cell Markers in Canine Oligodendrogliomas

Abstract

Oligodendroglioma is a common brain tumor in dogs, particularly brachycephalic breeds. Oligodendrocyte precursor cells (OPCs) are suspected to be a possible origin of oligodendroglioma, although it has not been well elucidated. In the present study, 27 cases of canine brain oligodendrogliomas were histologically and immunohistochemically examined. The most commonly affected breed was the French Bulldog ( n = 19 of 27, 70%). Seizure was the most predominant clinical sign ( n = 17 of 25, 68%). The tumors were located mainly in the cerebrum, particularly in the frontal lobe ( n = 10 of 27, 37%). All cases were diagnosed as anaplastic oligodendroglioma (AO) and had common histologic features characterized by the proliferation of round to polygonal cells with pronounced atypia and conspicuous mitotic activity (average, 10.7 mitoses per 10 high-power fields). Honeycomb pattern ( n = 5 of 27, 19%), myxoid matrix ( n = 10, 37%), cyst formation ( n = 6, 22%), necrosis ( n = 19, 70%), pseudopalisading ( n = 5, 18.5%), glomeruloid vessels ( n = 16, 59%), and microcalcification ( n = 5, 19%) were other histopathologic features of the present tumors. Immunohistochemically, the tumor cells were positive for Olig2 in all cases and for other markers of OPCs in most cases, including SOX10 ( n = 24 of 27, 89%), platelet-derived growth factor receptor α ( n = 24, 89%), and NG2 ( n = 23, 85%). The present AO also consisted of heterogeneous cell populations that were positive for nestin ( n = 13 of 27, 48%), glial fibrillary acidic protein ( n = 5, 19%), doublecortin ( n = 22, 82%), and βIII-tubulin ( n = 15, 56%). Moreover, cultured AO cells obtained from 1 case retained expression of OPC markers and exhibited multipotent characteristics in a serum culture condition. Overall, the findings suggest that transformed multipotent OPCs may be a potential origin of canine AO.

Canine Primary Intracranial Cancer: A Clinicopathologic and Comparative Review of Glioma, Meningioma, and Choroid Plexus Tumors

“…Importantly, all of the markers noted above are known to have marked variation in labeling patterns in necropsy samples (owing to variations in fixation time, autolysis, amount of formalin used, and other factors) and use of these markers in necropsy samples should be interpreted with caution (78). Immunohistochemical studies in canine oligodendrogliomas support that these tumors have a dedifferentiated phenotype, one that may arise from an oligodendrocyte precursor cell, perhaps specific to the subventricular zone (85). Some of the markers used to support the origin from oligodendrocyte precursor cells include SOX10, nestin, NG2, and doublecortin (85).…”

“…Immunohistochemical studies in canine oligodendrogliomas support that these tumors have a dedifferentiated phenotype, one that may arise from an oligodendrocyte precursor cell, perhaps specific to the subventricular zone (85). Some of the markers used to support the origin from oligodendrocyte precursor cells include SOX10, nestin, NG2, and doublecortin (85). In addition, canine gliomas express several neuronal markers including synaptophysin supporting an origin from a multipotential cell type (82).…”

Safety, Tumor Reduction, and Clinical Impact of Zika Virus Injection in Dogs with Advanced-Stage Brain Tumors

“…As requested by the owners and for ethical reasons, the Boxer dog was euthanized on day 153. Post-mortem histopathological tumor exam confirmed the diagnosis of oligodendroglioma based on cell markers profile: positive staining for Olg2, CD56, S100, and Ki67 markers, and negative staining for GFAP, Sinaptofisin, Neurofilament, and NSECK-Pan markers 14,15 ( Figure S2). Extensive necrosis, cellular debris, and immune-cellular infiltration were observed in tumor mass histopathological analysis ( Figure S3), including a central hole and macroscopic tissue degeneration ( Figure 2D), probably induced by ZIKV anti-tumoral effect since these features are unexpected in untreated oligodendroglioma.…”

Microtubule-Associated Protein 2 Expression in Canine Glioma

“…Current theories are focused on neural stem cells (23); however, there is strong evidence that mature astrocytes can dedifferentiate and regain immature glial properties and be a source of neoplastic transformation (25, 26). While the cell of origin remains unclear in the dog, canine oligodendrogliomas do express a number of immunohistochemical markers of oligodendrocyte precursor cells including SOX10 and NG2, supporting a role for altered progenitor cells in the pathogenesis (27).…”