Prognostic value of CXCL12 expression in 40 low-grade oligodendrogliomas and oligoastrocytomas

Abstract

Both clinical and biological features have been reported as prognostic factors in low-grade gliomas. Among these, histotype, tumor size, enhancement, age and genetic pattern. Microvessel density (MVD) has been correlated to clinical outcome in astrocytomas, but its impact in oligodendrogliomas and mixed tumors is not sure. The pro-angiogenic chemokine stromal cell-derived factor (SDF-1/CXCL12) and its receptor CXC chemokine receptor 4 (CXCR4) have been described in low-grade gliomas, with a correlation between CXCL12 expression and shorter time to progression (TTP). The intermediate filament Nestin is expressed in proliferating vessels. Platelet-derived growth factor B (PDGF-B) and its receptor PDGFR-β are also involved in angiogenesis and malignant progression in gliomas. The aim of this study was to retrospectively investigate the MVD and immunohistochemical expression of CXCL12, CXCR4, PDGF-B, PDGFR-β and Nestin in 40 patients (11 oligodendrogliomas and 29 oligoastrocytomas). In our study, oligodendroglioma histotype was associated with a trend to a more prolonged TTP than mixed tumors (P = 0.12). Age younger than 32, pre-surgery lack of enhancement at CT/MRI and total versus partial resection were not associated with longer TTP. Positivity for CXCL12 on tumor/endothelial cells was the only factor associated with a significantly shorter TTP (P = 0.011). Positivity for CXCL12 in tumor cells was predictive of a shorter survival time (P = 0.014). Since CXCL12 is not only related to angiogenesis, but also exerts an anti-apoptotic effect that may contribute to tumor progression/endothelial escape from apoptotic mechanisms, expression of CXCL12 by these tumors might add prognostic information to available clinical and bio-molecular indexes.