“Cyclooxygenase-2 (cox-2) expression in feline intracranial meningiomas”

Cyclooxygenase (COX, also called prostaglandin H synthase), is a bifunctional enzyme that catalyzes the conversion of arachidonic acid into prostaglandins. Currently, three COX isoenzymes are known: the COX-1 isoform is expressed constitutively, and is mainly associated with the production of prostaglandins involved in important physiological processes such as the cytoprotection of the gastric mucosa and renal blood flow; COX-3 is a splice variant of COX-1; the COX-2 isoform is inducible and is expressed in normal cells, such as macrophages, in response to pro-inflammatory stimuli and in multiple types of cancer cells, where it may mediate several oncogenic functions, including stimulation of proliferation and angiogenesis, inhibition of apoptosis, and immune suppression. Recent studies have demonstrated COX-2 expression in a variety of canine and feline tumors, including squamous-cell carcinoma, transitional-cell carcinoma, mammary gland carcinoma, melanoma, and osteosarcoma. Furthermore, strong COX-2 expression has been identified as a negative prognostic factor in several human neoplasms, as well as in canine and feline mammary tumors and in canine osteosarcoma. In human neurology, COX-2 is frequently expressed in the brain during different pathologic conditions. Numerous data show the presence of COX-2 in the glioma-affected brain and indicate the therapeutic effectiveness of COX inhibitors in the gliomas. COX-2 overexpression has been observed also in the majority of meningiomas, although the increasing immunohistochemical COX-2 expression was not constantly associated to malignancy grade. Furthermore, an association of COX-2 up-regulation to edema index, as revealed by CT scan, has been reported, suggesting a role of COX-2 also in the development of the brain edema associated to meningioma. Recently, COX-2 expression has been found also in 21 out of 24 canine intracranial meningiomas, with no significant association to tumor grade. Conversely, COX-2 expression has not been investigated yet in feline meningiomas. The aim of this study was to evaluate by immunohistochemistry the expression of COX-2 in a series of 35 intracranial feline meningiomas (20 biopsy and 15 post mortem samples) classified histologically according to the WHO system. Nineteen were transitional, seven fibroblastic, four psammomatous, four malignant, one meningothelial. The histological grade was I in 24 and II in 11 cases. Eight cases were also investigated with MRI, and moderate peritumoral edema was evident in only one of them (transitional histotype, grade I). COX-2 immunohistochemistry was carried out using a rabbit polyclonal antibody (Cayman Chemical) and prompted immunopositivity in 15 out of 35 feline meningiomas (43%). The immunoreactivity was cytoplasmic with occasional perinuclear reinforcement, and spread multifocally throughout the sections in meningothelial nests and small cellular aggregates. COX-2 immunopositivity was marked in only three cases, one grade I and two grade II meningiomas, and mild to moderate in the other cases. COX-2 was expressed also by intratumoral inflammatory cells in only one case (malignant histotype, grade II); the endothelial cells of peritumoral vessels and the adjacent normal brain tissue did not express COX-2. Pearson’s chi-square test did not show any correlation between COX-2 expression, tumor histotype and tumor grade. These findings suggest that COX-2 is expressed in feline meningiomas at low levels, if compared to COX-2 expression in canine and human meningiomas, suggesting a basic species disparity. Further investigations are required to support these preliminary results and to elucidate the actual role of COX-2 in the biological behavior of feline meningioma and the possible perspectives of COX-2 inhibitory treatment strategies.