engleski

The expression of osteopontin in human astrocytomas: interstitial expression correlates with malignancy grade and angiogenesis

Osteopontin (OPN) is a phosphorylated protein secreted into the extracellular matrix by a variety of cell types. Numerous functions have been ascribed to osteopontin, including roles in bone remodelling, cell-adhesion, cell-mediated immunity, the ability to act as a cytokine in cell signalling, resulting in proliferation and/or cell survival, and angiogenesis. OPN has also been detected in a number of human tumour tissues and assessed as a potential marker of tumour progression. This study was aimed to analyse by immunohistochemistry the expression of OPN in 76 human gliomas of various grades of malignancy: 8 pylocytic astrocytomas, 10 grade 2 astrocytomas, 8 anaplastic astrocytomas and 50 glioblastomas. The immunohistochemical staining results were scored in a semi-quantitative manner by assessing the percentage of positive tumour cells and the intensity of staining. We also assessed the intercellular distribution of staining, which was categorized as focal or diffuse, with the staining intensity expressed either as low or high. Since OPN has been implicated in angiogenesis, we analysed the correlation between OPN expression and microvessel densitiy in glioblastomas. Microvessels were immunohistochemically stained with &#61537; -endoglin antibody (CD105) and counted in predominantly vascular areas (hot spots) at x 400 magnification. Our results show that OPN protein is expressed in human astrocytic tumors and suggest the role of OPN in astrocytoma progression and angiogenesis. : In normal brain tissue the expression of OPN was present in some glial and neuronal cells in the form of cytoplasmyc granular staining of low intensity, while microglial cells were strongly positive. In glial tumors intracellular OPN expression was heterogenous, ranging from absent or low (score 0-5) to strong (score 6-10). Strong OPN expression was observed in 3 grade I (37.5%), 4 grade II (40%), 2 grade III (25%) and 21 grade IV (42%) astrocytomas. In some tumors OPN was also present interstitially, between tumor cells. This staining pattern was accentuated around tumor necrosis and, in most of the cases, also around blood vessels. Tumours with either a diffuse or strong expression were considered positive in intercellular distribution of OPN staining. Interstitial OPN expression was observed in 1 pylocytic astrocytoma (12.5%), 2 grade II astrocytomas (20%), 2 anaplastic astrocytomas (25%) and 25 glioblastomas (50%). We found the association of interstitial OPN expression and angiogenesis i.e. microvessel density was higher in tumors with high interstitial OPN expression (Mann Whitney test, p<0.03).

osteopontin; bone remodelling; gliomas; glioblastomas; cytokine; cell signalling; astrocytomas; glial tumors

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