Einfluss des vaskulären Permeabilitätsfaktor VEGF auf die Tumorzelldissemination bei Patienten mit Ösophaguskarzinom
VEGF does not only induce neo-angiogenesis of malignant tumors but also increases vascular permeability and might facilitate tumor cell dissemination. The expression of VEGF, microvessel count and the incidence of micro-disseminated tumor cells in lymph nodes and bone marrow were analysed immunohistochemically in 78 patients with esophageal cancer. VEGF was detected using a polyclonal anti-VEGF rabbit antibody while vascular density was assessed by endothelial staining with an anti-CD3l antibody. Isolated tumor cells in lymph nodes and bone marrow aspirates were detected using the antiepithelial antibodies Ber-EP4 and A45 respectively. In 50 (64.1%) patients a strong VEGF staining signal was detected, while 12 (15.4%) exhibited an intermediate and 16 patients (19.2%) a weak VEGF expression. The vascular density of the primary tumor was low in 16 (20%) patients, moderate in 23 (29.3%), intermediate in 26 (33.3%) and strong in 13 (17.3%) of the cases. Nodal micro-dissemination was detected in 52 (66.6%) patients while in 18 (42.9%) patients epithelial cells were found in bone marrow aspirates. Altered vascular density as well as the T-stage of the primary tumor exhibited a significant correlation with increased VEGF expression p = 0.003 and p = 0.001 respectively. However there was no association between VEGF and the incidence of lymphatic or haematogenous tumor cell dissemination. We concluded that local tumor progression is significantly associated with elevated VEGF expression. The relevance of this molecule for neoangiogenesis is underlined by the correlation with micro-vessel density. Despite of the increased vascular permeability caused by VEGF the influence on tumor cell dissemination seems to be low, as no association with the incidence of micro-dissemination was detectable.
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