The association between tumour progression and vascularity in the oral mucosa

Abstract

Tumourigenesis in experimental models is associated with the formation of new blood vessels (angiogenesis). Recent studies have suggested that tumour angiogenic activity may be inferred in histological sections by measuring the density of the vasculature. The purpose of this study was to determine whether the transition from normal to dysplastic and neoplastic tissue in the oral mucosa is accompanied by quantitative or qualitative changes in the vascularity of the tissue, and how the estimate of vascularity is influenced by the vessel marker and method of assessment. A total of 100 specimens of normal oral mucosa, dysplastic lesions, and squamous cell carcinomas were examined. Sections were immunostained with the pan‐endothelial antibodies to von Willebrand Factor (vWF) and CD31, or with an antibody to the αvβ3 integrin, previously reported to be a marker of angiogenic vessels. Vascularity was quantitated by two different methods: highest microvascular density (h‐MVD) and microvascular volume, as determined by point counting (MVV). The results showed that vascularity, measured by the MVV method using antibodies to either vWF or CD31, increased significantly (P<0·0001) with disease progression from normal oral mucosa, through mild, moderate, and severe dysplasia to early and late carcinoma (76 paraffin‐embedded tissues examined). In contrast, h‐MVD did not discriminate between dysplastic lesions and carcinoma. A similar percentage of the total vessel volume (MVV) and density (h‐MVD) were positive for αvβ3 in 24 frozen tissues examined, including normal oral mucosa. It is concluded that there is a close association between vascularity and tumour progression in the oral mucosa. Morphometric analysis reflecting microvascular volume is more informative than the currently popular analysis of microvascular density. The expression of αvβ3 in the vasculature of oral tissues does not necessarily reflect the presence of angiogenic vessels. © 1997 by John Wiley & Sons, Ltd.

Prognostic significance of VEGF immunohistochemical expression and tumor angiogenesis in head and neck squamous cell carcinoma

“…High microvessel density was associated with metastasis and/or a worse clinical outcome in many studies (Shpitzer et al 1996;Pazouki et al 1997;Penfold et al 1996;Williams et al 1994), but this observation was not confirmed in several other studies (Dray et al 1995;Gleich et al 1996;Janot et al 1996;Moriyama et al 1997). Our results suggest a correlation of MVD with clinical stage.…”

“…Studies examining the association of VEGF immunohistochemical expression and tumor angiogenesis with clinicopathological factors and outcome in head and neck squamous cell carcinoma (HNSCC) have yielded inconclusive and conflicting results (Leedy et al 1994;Dray et al 1995;Gleich et al 1996;Shpitzer et al 1996;Pazouki et al 1997;Penfold et al 1996;Salven et al 1997;Maeda et al 1998;Neuchrist et al 1999;Smith et al 2000;Aebersold et al 2000;Gallo et al 2001;Mineta et al 2002;Dunphy et al 2002). These discrepancies may be caused by differences in tumor location, the choice of antibodies, and cutoffs as well as variability in IHC protocols (Vermeulen et al 2002;Hannen et al 2002).…”

Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma

“…There have been a number of studies evaluating the prognostic significance of microvessel density in head and neck squamous cell carcinoma [1,15,23,24,32,37] with conflicting and contradictory results. In all of these reports, investigators used pan-endothelial markers, namely, CD34, CD31, and von Willebrand factor, to highlight microvessels.…”

Expression of vascular endothelial growth factor (VEGF) in normal oral mucosa, oral dysplasia and oral squamous cell carcinoma

“…Angiogenesis, the formation of new blood vessels, is crucial to the growth, invasion and metastasis of a tumour 6,8 . A significant increase in vascularity occurs during the transition from normal oral mucosa (NOM), through differing degrees of dysplasia, to invasive squamous cell carcinoma (SCC) 2,12,17 . This increase in vascularity has been associated with tumour progression from early to late carcinoma 17 and lymph node metastasis 18 .…”

“…A significant increase in vascularity occurs during the transition from normal oral mucosa (NOM), through differing degrees of dysplasia, to invasive squamous cell carcinoma (SCC) 2,12,17 . This increase in vascularity has been associated with tumour progression from early to late carcinoma 17 and lymph node metastasis 18 . Previous research has shown that an adequate blood supply is essential for solid tumour growth and metastasis 7 .…”