Tumor vascularity: A histological measure of angiogenesis and hypoxia

In this study we sought to clarify the relationship between tumor vasculari ty, hypoxia, and angiogenesis in human cervix tumors. Two hypotheses were e stablished: first, that measurement of tumor vascularity can provide a hist ological assessment of both hypoxia and angiogenesis; and second, that expr ession of angiogenesis-related proteins will provide a surrogate measure of tumor hypoxia, To test the first hypothesis, we studied the prognostic sig nificance of tumor vascularity measured as both intercapillary distance (IC D; thought to reflect turner oxygenation) and microvessel density (MVD; the hotspot method that provides a histological assessment of tumor angiogenes is), The relationship was also examined of turner hypoxia, measured using a n Eppendorf needle electrode [percentage of values less than 5 mm Hg (Hp5)] , with ICD and MVD. To test the second hypothesis we examined the relations hip between HP5 and the expression of angiogenesis-associated proteins [vas cular endothelial growth factor (VEGF) and platelet-derived endothelial cel l growth factor (PD-ECGF)]. All of the biological measurements were made on pretreatment tumors. Analysis of data was carried out using log- rank stat istics, Cox multivariate analysis, and Spearman's rank correlation. Both IC D and MVD were significant independent prognostic factors for local control . Patients with poorly vascularized tumors (long ICD) had poor local contro l (P = 0.042). However, patients with poorly vascularized tumors, measured as low MVD, had good local control (P = 0.036). For 107 patients in whom bo th of the measurements were obtained on the same tumor sections, ICD and MV D provided independent prognostic information in multivariate analysis. The re was a significant correlation between tumor hypoxia and ICD (P < 0.005) but not MVD (P = 0.41). There was no relationship between hypoxia and the e xpression of angiogenic factors (VEGF, PD-ECGF), These analyses show that m easurement of tumor vascularity can provide different biological informatio n that is dependent on the method used. It is, therefore, important that st udies measuring vascularity should include an appropriate definition. There is no relationship between hypoxia and angiogenesis in advanced carcinoma of the cervix and examining the levels of angiogenic proteins may not have a role in assessing hypoxia in cervix cancer.