Tumor Angiogenesis in Oral Squamous Cell Carcinomas: The Significance of Endothelial Markers and Hotspot Selection

Abstract

The intensity of angiogenesis affects the prognosis for many malignant tumors, but there is no consensus about the association between the prognosis of oral squamous cell carcinoma (OSCC) and the intensity of angiogenesis. This discrepancy might be caused by different endothelial markers used and by hotspot selection. The aim of this study was to investigate the sensitivity and specificity of different endothelial markers for evaluating microvessel density (MVD) in OSCCs. We also examined the effect of hotspot area selection in association with clinicopathological features of OSCCs. Methods: We collected 84 OSCC specimens for immunohistochemical staining for three common endothelial makers: van Willebrand factor (vWF), CD31 and CD34. Peritumoral and intratumoral vascular hotspot areas were selected separately for MVD counting. Results: There was no significant association between peritumoral MVD and clinicopathological parameters. However, the intratumoral MVDs determined using CD31 and CD34 were significantly associated with tumor size (P=0.003 and P＜0.0001, respectively), with histological differentiation (P=0.0025 and P=0.018, respectively) and with tumor stage (P=0.001 and P＜0.0001, respectively). In addition, the intratumoral MVD counted using CD34 immunostaining was significantly associated with lymph node metastasis of OSCC (P=0.005). Conclusions: Tumor angiogenesis and the density of newly formed vessels are of potential prognostic relevance in the assessment of malignant neoplasia. The endothelial marker CD34 was better in the assessment of tumor vascularization of OSCCs. Furthermore, hotspot selection, especially intratumoral MVD, is important in examining OSCC progression.