VEGFR1 and VEGFR2 immunohistochemical expression in oral squamous cell carcinoma: a morphometric study.

Vascular endothelial growth factor (VEGF) is considered one of the main molecules involved in tumor angiogenesis and is largely expressed in oral squamous cell carcinoma (OSCC). His signal is transmitted intracellulary by binding with class III tyrosine kinase receptors, known as VEGF receptor family (VEGFRs). Therefore, we designed this study for quantification of VEGFR1 and VEGFR2 immunohistochemical expression in the tumor cells of OSCC, and compare this expression with clinicopathologic parameters. For this purpose, 46 formalin-fixed, paraffin-embedded tissue blocks of OSCC were processed by immunohistochemistry. The immunohistochemical signal was assessed by estimating the area of the objects and the medium pixel intensity per object, as the integrated optical density (IOD). In our study, VEGFR1 staining intensity was significantly higher for tongue localization, while VEGFR2 was higher for the lip. Both markers were higher expressed in the center of the tumor compared to the tumor front. Moderate differentiated tumors exert higher expression levels for VEGFR1 but lower for VEGFR2. pT1 tumors had higher VEGFR1 levels, and when lymph node involvement was present, this was accompanied by elevated expression levels for VEGFR2 and lower levels for VEGFR1. These results point to an inverse profile of these receptors in OSCC, suggesting their involvement in a sequential manner in VEGF signaling regulation. In conclusion, our study revealed that VEGFR1 and VEGFR2 correlate with tumor localization, tumoral area (front vs. center of the tumor), histological differentiation degree, and lymph node involvement, while only VEGFR1 correlated with pT stage.

VEGF and VEGFRs expression in oral squamous cell carcinoma.

Oral cancer is an important cause of worldwide morbidity and mortality, with substantial economic, physiological, and psychosocial impacts due to its treatment modality and a great risk for recurrences and second primary oral squamous cell carcinomas (OSCC) development. Therefore, it is very important to understand the underlying cell biology of such tumors. It is now a well-accepted fact that angiogenesis is essential for the growth and metastasis of solid tumors, including head and neck squamous cell carcinoma. The main factor responsible for angiogenesis is VEGF and its receptors. It has been demonstrated that VEGFRs are also present on tumor cells themselves and other cells from the tumor microenvironment, in addition to tumoral endothelial cells (ECs). Therefore between these cells take place numerous and different interactions mediated via paracrine/autocrine pathways that promote angiogenesis, uncontrolled tumor proliferation and metastasation. In consequence, estimation of VEGF expression and its receptors became a reliable prognostic tool in OSCCS, predicting the poor disease-free survival, poor overall survival, and metastatic disease. Understanding the distribution and role of VEGF and its receptors in the progression of OSCC will be essential to the development and design of new therapeutic strategies.