Apoptosis, proliferation, and angiogenesis in oral tissues. Possible relevance to tumour progression

Experimental animal models have demonstrated that angiogenesis is essential for tumour progression, whilst sustained tumour growth requires a positive balance between tumour cell proliferation and cell death (apoptosis). The aim of this study was to determine the relative contribution of apoptosis, proliferation, and angiogenesis to disease progression in the oral mucosa. Histological sections of 47 archival specimens were examined; these include d four groups of oral tissues: normal mucosa (n = 12), moderate dysplasia ( n = 11) severe dysplasia (n = 6), and squamous cell carcinoma (n = 18). Apo ptotic cells were visualized by in-situ end-labelling of DNA, proliferative cells by staining with Ki-67 antibody, and blood vessels with von Willebra nd factor (VWF) antibody. One-way analysis of variance showed that indices of apoptosis (AI), proliferation (PI), and angiogenesis (vascularity) incre ased significantly with disease progression from normal oral mucosa, throug h dysplasia, to carcinoma (p < 0.0001 for every index). The increase from n ormal mucosa to moderate dysplasia was significant for PI and vascularity, but not for AI. In contrast, the increase from dysplasia to carcinoma was s ignificant for AI and vascularity, but not for PI. These data suggest that disease progression in the oral mucosa is accompanied by angiogenesis and i ncreases in both epithelial proliferation and apoptosis. Net epithelial gro wth results from proliferation starting earlier and proceeding at a higher rate than apoptosis, Copyright (C) 2000 John Wiley & Sons, Ltd.