[Show abstract][Hide abstract] ABSTRACT: Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including angiogenesis, cancer development, invasion and metastasis. The aim of the study was to analyze the expression of OPN in human astrocytomas and to correlate it with angiogenesis and patients' outcome. Seventy-six human astrocytomas including eight pilocytic astrocytomas (grade I), 10 diffuse astrocytomas (grade II), 8 anaplastic astrocytomas (grade III) and 50 glioblastomas (grade IV) were immunohistochemically stained for OPN protein. The distribution of OPN staining (cytoplasmic and/or interstitial) was assessed and compared to microvessel number and patients' survival. In normal brain tissue some glial and neuronal cells showed weak cytoplasmic staining, while interstitium was negative. Astrocytomas were heterogeneous regarding the OPN expression. High cytoplasmic OPN expression in glioblastomas was associated with poor patients' survival (p = 0.012). Also, we found the association of interstitial OPN expression and angiogenesis (p = 0.033), i.e. the number of newly formed blood vessels was higher in tumors showing high interstitial OPN expression. Our results indicate the overexpression of OPN protein in astrocytoma cells and suggest the role of OPN in astrocytoma progression and angiogenesis.
Pathology & Oncology Research 06/2008; 14(3):293-8. · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare endoglin (CD105) and the pan-endothelial marker CD31 in the assessment of angiogenesis in glioblastoma and to evaluate their values in the prognosis of this malignancy.
Forty-six cases of glioblastoma were included in this retrospective study. All cases were immunohistochemically stained for endoglin (CD105), CD31, vascular endothelial growth factor (VEGF), and MIB-1 (Ki67). In order to assess microvessel density, positively stained microvessels were counted for each specimen in predominantly vascular areas (hot spot) at x400 magnification. The intensity of VEGF staining was scored on a three-tiered scale. The proliferation index was expressed as a percentage of Ki67 positive cells.
Median CD105 microvessel density (median 49 microvessels/field, range 27-99) was significantly higher than median CD31 microvessel density (median 37 microvessels/field, range 12-76). CD105 microvessel density was more closely correlated with VEGF (Spearman's rho=0.421, P=0.003) than with CD31 microvessel density (rho=0.330, P=0.024). The proliferation index was significantly associated with CD105 microvessel density (Pearson's r=0.323, P=0.028), whereas correlation could not be observed with CD31 microvessel density (r=0.219, P=0.142). Finally, patients with lower CD105 microvessel density had a longer survival than those with higher CD105 microvessel density (P=0.045), whereas CD31 microvessel density had no influence on the survival time (P=0.340).
CD105 is a more sensitive marker than CD31 in the evaluation of angiogenesis in glioblastoma. Our study is the first report of the better prognostic significance of angiogenesis evaluated with CD105 rather than with CD31 in glioblastoma.
Croatian Medical Journal 07/2005; 46(3):417-22. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tenascin-C (TN-C) is an extracellular matrix protein which participates in different processes like normal fetal development, wound healing, inflammation, keloids and rheumatoid arthritis. Furthermore, the immunostaining for TN-C is seen in the stroma of various malignant tumors as in glioblastoma multiforme (GBM), however, the significance of these findings is still not clear. In this study 62 GBM samples were analyzed immunohistochemically for distribution patterns of TN-C and correlated with angiogenesis and tumor cell proliferation. Tenascin-C in GBM localizes in two compartments, perivascular and intercellular space. Intercellular tenascin-C (TN-C ic) showed focal distribution in 66%, and diffuse one in 34% of cases. Perivascular tenascin-C (TN-C pv) showed strong correlation with microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression. Moreover, it seems that TN-C pv enhanced the effect of VEGF. Intercellular TN-C did not correlate with MVD and VEGF expression, but showed strong correlation with proliferation index. Furthermore, tumors with diffuse TN-C ic expression had higher proliferation indices than tumors with focal TN-C expression. Our results indicate that TN-C plays a role in angiogenesis and tumor cell proliferation, but beside the intensity of expression, the distribution patterns are also important in these processes. This study also suggests that perivascular and intercellular TN-C compartments have probably different sources and different roles in GBM.
Pathology & Oncology Research 02/2005; 11(4):229-35. · 1.56 Impact Factor