Microtubule-Associated Protein 2 Expression in Canine Glioma

Abstract

Canine glioma is considered a potential model for human glioma, with recent studies of occurrence, therapy, and reclassification supporting the value of the canine model. The current diagnosis of canine glioma is based on morphologic criteria and immunohistochemistry (IHC), including oligodendrocyte transcription factor 2 (Olig2), glial fibrillary acidic protein (GFAP), and 2', 3' cyclic nucleotide phosphatase (CNPase). Microtubule-associated protein 2 (MAP2) is a proven marker of human glioma and is used to complement the diagnosis and its specific immunoreactivity pattern contributes to the differentiation of astrocytomas from other glial tumors. The objective of this study was to evaluate whether canine gliomas express MAP2 and to explore differences in the pattern of immunolabeling between different gliomas. Seventy-eight cases of canine glioma were evaluated for MAP2 expression by immunohistochemistry. A glial origin was supported by Olig2 IHC in all cases. MAP2 immunolabeling was evaluated on a semi-quantitative basis, including the percentage of immunolabeled neoplastic cells, as well as the signal intensity, distribution, and pattern of immunolabeling. MAP2 was expressed in all cases, with significant correlation between diagnosis and signal intensity (P = 0.04). MAP2 immunolabeling distribution was dominated by diffuse (34/78; 44%), followed by patchy (20/78; 26%), multifocal to coalescing (16/78; 21%), and scattered (8/78; 10%). All oligodendrogliomas (53/53; 100%) and undefined gliomas (12/12; 100%) revealed a combination of perinuclear and cytoplasmic immunolabeling, and all but 3 astrocytomas had a combination of perinuclear and cytoplasmic processes immunolabeling (10/13; 77%). Significant correlation between immunolabeling pattern and diagnosis was obtained (P = 0.001). The study demonstrates that MAP2 is expressed in canine gliomas and the pattern of expression can also be applied to help distinguish astrocytomas from oligodendrogliomas and undefined gliomas.

Keywords: astrocytoma; canine; glioma; immunohistochemistry; microtubule-associated protein 2; oligodendroglioma.

Figure 1

(A) Canine, Oligodendroglioma. Sheets of neoplastic oligodendrocytes with nuclear rowing and sparse stroma with branching capillaries (Hematoxylin and eosin (H&E) stain). (B) Canine, Oligodendroglioma. Round nuclei with coarse chromatin (H&E stain). (C) Canine, Oligodendroglioma. Diffuse immunolabeling with strong signal intensity (score 3) (Immunohistochemistry (IHC); MAP2). (D) Canine, Oligodendroglioma. Multifocal to coalescing distribution with moderate signal intensity (score 2) (IHC; MAP2). (E) Canine, Oligodendroglioma. Multifocal patchy immunolabeling with moderate signal intensity (score 2) (IHC; MAP2). (F) Canine Oligodendroglioma. Perinuclear and cytoplasmic immunolabeling pattern present in all cases of oligodendroglioma (IHC; MAP2).

Figure 2

(A) Canine, Astrocytoma. Low-magnification of an astrocytoma (Hematoxylin and eosin (H&E) stain). (B) Canine, Astrocytoma. Low-magnification of MAP2 immunolabeling in an astrocytoma revealing multifocal to coalescing distribution with score 2 signal intensity (Immunohistochemistry (IHC); MAP2). (C) Canine, Astrocytoma. Low degree of cellular density, pleomorphism, and angular nuclei. (H&E stain). (D) Canine, Astrocytoma. Diffuse distribution of MAP2 immunolabeled cells in a case scored as a 3 for percent of neoplastic cells with immunolabeling (IHC; MAP2). (E) Canine, Astrocytoma. Patchy, multifocal distribution of MAP2 immunolabeled neoplastic cells (IHC; MAP2). (F) Canine, Astrocytoma. Immunolabeling of cytoplasmic processes (CtP) and perinuclear (PNc), a pattern noted in the majority of canine astrocytomas (IHC; MAP2.).

Figure 3

(A) Canine, Undefined glioma. Biphasic or biphenotypic morphology with palisading neoplastic cells around areas of necrosis. (Hematoxylin and eosin (H&E) stain). (B) Canine, Undefined glioma. Combination of nuclear rowing, pleomorphism, and high mitotic count (H&E stain). (C) Canine, Undefined glioma. MAP2 immunolabeling of canine undefined glioma revealing diffuse distribution with a score 3 signal intensity (Immunohistochemistry (IHC); MAP2). (D) Canine, Undefined glioma. Scattered distribution with a score 2 signal intensity (IHC; MAP2). (E) Canine, Undefined glioma. Scattered distribution with a score 1 signal intensity (IHC; MAP2). (F) Canine, Undefined glioma. The immunolabeling pattern, perinuclear (PNc) and cytoplasmic (Ct), noted in all undefined gliomas (IHC; MAP2).