Inverse correlation of apoptotic and angiogenic markers in squamous cell carcinoma of the head and neck

Angiogenesis is essential for tumour growth and metastasis. The induction of tumour vascularization is mediated by the release of angiogenic peptides. Among these factors, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are thought to be the most important. Previous experimental studies indicate that the process of apoptosis, the programme of cell death, may be related to angiogenesis in head and neck carcinogenesis. Therefore, cryostat sections of 49 head and neck squamous cell carcinomas (HNSCC) were investigated immunohistochemically for pro-apoptotic factors caspase-3 and Fas ligand (FasL) using a standard streptavidin-biotin complex procedure. Expression of bFGF, VEGF and MMP-9 served as angiogenic markers. Additionally, intratumoral microvascular density (MVD) was counted by immunostaining of endothelial cells using anti-vWF antibody. Comparing the expression of apoptotic and angiogenic factors, a statistically significant inverse correlation of caspase-3 expression and VEGF and MMP-9 expression was found. Concerning FasL, the correlation of its expression with expression of VEGF, bFGF and MMP-9 was inversely correlated. With respect to vWF-immunostaining, statistical analysis gave a clear inverse correlation between the tumour vascularity and the expression of FasL (p=0.0008) and caspase-3 (p=0.0068). Our results suggest that HNSCC tumour angiogenesis contributes to a reduction of apoptosis in tumour cells. This may be explained by the activation of pro-apoptotic factors caused by hypoxia.