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

Abstract

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 included four groups of oral tissues: normal mucosa (n=12), moderate dysplasia (n=11) severe dysplasia (n=6), and squamous cell carcinoma (n=18). Apoptotic cells were visualized by in-situ end-labelling of DNA, proliferative cells by staining with Ki-67 antibody, and blood vessels with von Willebrand factor (vWF) antibody. One-way analysis of variance showed that indices of apoptosis (AI), proliferation (PI), and angiogenesis (vascularity) increased significantly with disease progression from normal oral mucosa, through dysplasia, to carcinoma (p<0.0001 for every index). The increase from normal mucosa to moderate dysplasia was significant for PI and vascularity, but not for AI. In contrast, the increase from dysplasia to carcinoma was significant for AI and vascularity, but not for PI. These data suggest that disease progression in the oral mucosa is accompanied by angiogenesis and increases in both epithelial proliferation and apoptosis. Net epithelial growth results from proliferation starting earlier and proceeding at a higher rate than apoptosis.

The expression of p53-induced protein with death domain (Pidd) and apoptosis in oral squamous cell carcinoma

“…The amount of apoptosis seen in carcinomas varied ( Figure 1B), with a range of apoptotic indices from 0.03 to 2.25%. The amount of apoptosis that we observed in the TUNEL assay was generally similar to that reported by others (Xie et al, 1999;Macluskey et al, 2000;Stoll et al, 2000). The late stages of apoptosis that result in the distinctive morphology of an apoptotic cell are thought to occur rapidly, followed by phagocytic removal of the apoptotic bodies by neighbouring cells.…”

Role of angiogenesis in oral squamous cell carcinoma development and metastasis: an immunohistochemical study

“…Previous studies have shown that vascularity increased in a stepwise fashion from normal mucosa through dysplasia to carcinoma, suggesting that disease progression in the oral mucosa is accompanied by angiogenesis [4][5][6][7][8][9]. In contrast our study showed no significant difference in vascularity between normal mucosa and leukoplakia, but a statistically significant difference was found between normal mucosa vs. carcinoma (P<0.001), and leukoplakia vs. carcinoma (P<0.001).…”

“…The expression of angiogenic activity has been shown to be an early and predictable characteristic of many pre-neoplastic cells, and may represent one of the earliest indications that a cell population has become committed to malig-nancy [3]. Studies have shown that vascularity increases from normal mucosa to moderate dysplasia to carcinoma [4][5][6][7][8][9]. Head and neck squamous cell carcinoma (HNSCC) have a high tendency to spread to adjacent sites and to the cervical lymph nodes (LNs), whereas their distant metastatic potential is very low [10].…”

The Relevance of Mast Cells in Oral Squamous Cell Carcinoma

“…By using an experimental animal model, it was shown that the initiation of angiogenesis appeared concomitantly with a decrease in the tumour cell apoptosis, while the levels of the tumour cell proliferation remained constant, thus leading to the net tumour growth [10]. The preinvasive malignant cells are known to remain dormant until they become angiogenic, and this is followed by a phase of rapid tumour growth [15,16].…”