Angiogenic factor VEGF is decreased in human colorectal neoplasms showing DNA microsatellite instability

Vascular endothelial growth factor (VEGF) and basic fibroblast growth facto r (bFGF) are two important determinants of angiogenesis in human cancers. E xpression of VEGF and bFGF was examined by immunohistochemistry in 120 colo rectal cancers. Neoplasms were classified according to the presence or abse nce of microsatellite instability determined at six microsatellite loci and labelled as a high microsatellite instability (MSI-H), low microsatellite instability (MSI-L) or microsatellite stable (MSS). Only 4/30 MSI-H cancers expressed VEGF (13 per cent), compared with 24/64 MSS cancers (38 per cent ; p<0.01). Fewer MSI-H cancers showed bFGF expression (38 per cent) than MS S cancers (53 per cent; p<0.09). MSI-L cancers showed the same pattern as M SS cancers. Western blotting and immunohistochemistry showed that the tumou r suppressor gene p53 was mutated infrequently in MSI-H cancers (8 per cent ; p<0.001). Microvessel density counts using CD31 and UEA-1 demonstrated no difference in the number of blood vessels in MSI-H and MSS cancers. Althou gh these results are consistent with the known role of wild-type p53 in dow n-regulating VEGF, no association was found between a mutation in p53 and V EGF or bFGF levels in all colonic neoplasms. This is the first evidence tha t MSI-H cancers may follow a different pathway to angiogenesis. The low fre quency of VEGF expression amongst MSI-H cancers may partially explain why t hese cancers are less aggressive, with a better overall prognosis. Copyrigh t (C) 1999 John Wiley & Sons, Ltd.