Angiogenic cytokines in mesothelioma: A study of VEGF, FGF-1 and-2, and TGF beta expression

Vascular endothelial growth factor (VEGF), acidic and basic fibroblast grow th factors (FGF-1 and -2), and transforming growth factor beta (TGF beta) a re potent angiogenic cytokines, Malignant mesothelioma of the pleura presen ts with a high intra-tumoural microvascular density (IMD) which also has pr ognostic relevance, This study was designed to verify the immunohistochemic al expression of the angiogenic cytokines in mesothelioma as well as in non -neoplastic human mesothelial cells and to study the individual as well as the combined expression of these cytokines in mesothelioma in relation to b oth IMD and prognosis. In addition, four mesothelioma cell lines were studi ed by ELISA for the secretion of VEGF and FGF-2 in their supernatants and w ere shown to contain high levels of both of these cytokines, Immunohistoche mically, VEGF, FGF-1 and -2, and TGF beta immunoreactivity was present in 8 1, 67, 92 and 96 per cent of mesotheliomas, and in 20, 50, 40, and 10 per c ent of samples of the non-neoplastic mesothelium, respectively, Go-ordinate expression of the cytokines was observed,whereby mesotheliomas expressed m ore than one cytokine. The combined immunohistochemical expression levels f or all four cytokines correlated significantly with both IMD (p = 0.01) and prognosis (p = 0.0013), When studied individually, high FGF-2 expression c orrelated best with more tumour aggressiveness and worse prognosis for meso thelioma (p = 0.0011). There was no significant correlation between prognos is and immunoexpression of VEGF (p = 0.07), FGF-1 (p = 0.3), or TGF beta (p = 0.1), or between IMD and any of the cytokines studied individually. Thes e data support the assertion that selective angiogenic cytokines might cont ribute to the progressive changes of mesothelioma by tumour angiogenesis. C opyright (C) 1999 John Wiley & Sons, Ltd.