Expression of Cell Adhesion Molecules and Doublecortin in Canine Anaplastic Meningiomas

Abstract

Tumor cell invasion into the surrounding nervous tissue is one of the histologic hallmarks of anaplastic meningiomas. To identify other possible markers for aggression in canine meningiomas, the relationship between histologic features and the expression of molecules involved in cell adhesion, cell proliferation, and invasion was examined. Immunohistochemistry for epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), b-catenin, doublecortin (DCX), and Ki-67 was performed for 55 cases of canine meningioma. DCX was preferentially expressed in tumor cells invading the brain parenchyma (12 of 14 cases), suggesting its involvement in the invasion process. Regardless of the histologic type, E-cadherin and N-cadherin expression was observed in 31 of 55 and 44 of 55 cases, respectively. There was a significant positive correlation between DCX and N-cadherin expression and a significant negative correlation between E-cadherin and N-cadherin expression, suggesting that decreased E-cadherin and increased N-cadherin expression induce DCX expression. Typical membranous b-catenin expression was observed in 10 of 55 cases, whereas nuclear translocation was observed in 33 cases. Nuclear b-catenin expression was frequently found in anaplastic meningiomas (12 of 14 cases). The Ki-67 labeling indices were significantly higher in anaplastic meningiomas than in other types. These findings indicate that the expression of N-cadherin and DCX and the nuclear translocation of b-catenin are closely associated with the presence of invasion and anaplasia in canine meningiomas. Notably, granular cell meningiomas were negative for almost all the molecules examined, suggesting that they have a different tumor biology than other meningiomas.

Spinal Meningeal Oligodendrogliomatosis in Two Boxer Dogs

“…7 Doublecortin is a microtubule-associated protein that is expressed in migrating neurons during development and is highly expressed in invasive brain tumors in humans. 2 Ide et al 3,4 reported the overexpression of doublecortin in canine oligodendroglioma and anaplastic meningiomas. 3 Neoplastic cells in both dogs of this report expressed doublecortin and Olig2, suggesting that the neoplastic cells had a low degree of differentiation and were of oligodendroglial origin.…”

Diagnostic Immunohistochemistry of Canine and Feline Intracalvarial Tumors in the Age of Brain Biopsies

“…9 Additional stem cell markers include nestin, beta III tubulin, and doublecortin, in line with the primitive nature of these tumors. 49 Doublecortin is a regulator of cytoskeletal organization and is involved in neuronal and glial migration; 24 mutations in this gene may result in developmental anomalies such as polymicrogyria. Nestin is an intermediate filament of immature neuronal cells active during development, but it does not separate neuronal and glial tumors in people.…”

“…Doublecortin, not expressed in normal meninges, might with further study become a useful tumor boundary marker. 49 The expression of vascular endothelial growth factor isoforms has been associated with peritumoral edema in a variety of canine brain tumors, but expression in meningiomas is low compared to that observed in high-grade parenchymal tumors. 22 Those meningiomas possessing high levels of vascular endothelial growth factor expression had shorter survival, which may be related to increased tumor vascularity.…”

Papillary meningioma in the dog: A clinicopathological case series study

“…To improve the knowledge on the biological behavior of meningioma, in the last years the expression of a series of molecules associated with cell adhesion and invasion have been investigated in human and canine meningiomas (Akat et al, 2008;Daou et al, 2005;Ide et al, 2011;Panagopolous et al, 2008;Shimada et al, 2005). Doublecortin (DCX), which plays a crucial role in neuroblast migration during the development of the cerebral cortex, is highly expressed in invasive brain tumors (Daou et al, 2005).…”