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 o f tumour vascularization is mediated by the release of angiogenic peptides. Among these factors, basic fibroblast growth factor (bFGF), vascular endot helial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) are thou ght to be the most important. Previous experimental studies indicate that t he process of apoptosis, the programme of cell death, may be related to ang iogenesis in head and neck carcinogenesis. Therefore, cryostat sections of 49 head and neck squamous cell carcinomas (HNSCC) were investigated immunoh istochemically for pro-apoptotic factors caspase-3 and Fas ligand (FasL) us ing a standard streptavidin-biotin complex procedure. Expression of bFGF, V EGF and MMP-9 served as angiogenic markers. Additionally, intratumoral micr ovascular density (MVD) was counted by immunostaining of endothelial cells using anti-vWF antibody. Comparing the expression of apoptotic and angiogen ic factors, a statistically significant inverse correlation of caspase-3 ex pression and VEGF and MMP-9 expression was found. Concerning FasL, the corr elation of its expression with expression of VEGF, bFGF and MMP-9 was inver sely correlated. With respect to vWF-immunostaining. statistical analysis g ave a clear inverse correlation between the tumour vascularity and the expr ession 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 fact ors caused by hypoxia.