Expression and association of vascular endothelial growth factor, vascular endothelial growth factor receptor, and phosphorylated signal transducer and activator of transcription factor 3 in malignant gliomas.

Abstract

Angiogenesis is one of the main characteristic features of malignant gliomas. Phosphorylated signal transducer and activator of transcription factor 3 (pSTAT3) is not only involved in glioma cell proliferation, anti-apoptosis, and immunosuppression but also plays a key role in cell migration and invasion. Constitutively, activated pSTAT3 induces expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR, leading to endothelial cell proliferation and abnormal microvascular formation causing peritumoral edema (PTE). PTE is one of the significant contributors to mortality in malignant gliomas. Therefore, understanding the molecular mechanism involved in the evolution of gliomas is necessary. This study was to assess the level of expression of pSTAT3, VEGF, and VEGFR in malignant gliomas and analyze the extent of PTE and the extent of expression of one or more of these markers. This study included 84 patients categorized as per the World Health Organization classification of central nervous system tumors into grade IV, III, and II gliomas to investigate the expression of pSTAT3, VEGF, and VEGFR by immunohistochemistry. Furthermore, the presence or absence of PTE was determined using magnetic resonance imaging/computed tomography scans in these patients. The association between the markers (pSTAT3, VEGFR, and VEGF) and the extent of PTE in these patients was statistically significant (P < 0.05). The pSTAT3, VEGF-R, and VEGF signaling pathways could contribute to peritumoral edema and might be a regulatory mechanism during PTE formation during tumorigenesis and progression.