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

Wynter, C. V. A., Simms, L. A., Buttenshaw, R. L., Biden, K. G., Young, J., Leggett, B. A., Conrad, R. J., Schoch, E. M., Jass, J. R. and Pillay, S. P. (1999) Angiogenic factor VEGF is decreased in human colorectal neoplasms showing DNA microsatellite instability. Journal of Pathology, 189 3: 319-325. doi:10.1002/(SICI)1096-9896(199911)189:3<319::AID-PATH436>3.3.CO;2-U


Author Wynter, C. V. A.
Simms, L. A.
Buttenshaw, R. L.
Biden, K. G.
Young, J.
Leggett, B. A.
Conrad, R. J.
Schoch, E. M.
Jass, J. R.
Pillay, S. P.
Title Angiogenic factor VEGF is decreased in human colorectal neoplasms showing DNA microsatellite instability
Journal name Journal of Pathology   Check publisher's open access policy
ISSN 0022-3417
Publication date 1999-01-01
Sub-type Article (original research)
DOI 10.1002/(SICI)1096-9896(199911)189:3<319::AID-PATH436>3.3.CO;2-U
Volume 189
Issue 3
Start page 319
End page 325
Total pages 7
Place of publication England
Publisher John Wiley & Sons
Language eng
Subject C1
321020 Pathology
730108 Cancer and related disorders
Abstract Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two important determinants of angiogenesis in human cancers. Expression of VEGF and bFGF was examined by immunohistochemistry in 120 colorectal cancers. Neoplasms were classified according to the presence or absence 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 MSS cancers (53 per cent; p<0.09). MSI-L cancers showed the same pattern as MSS cancers. Western blotting and immunohistochemistry showed that the tumour 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. Although these results are consistent with the known role of wild-type p53 in down-regulating VEGF, no association was found between a mutation in p53 and VEGF or bFGF levels in all colonic neoplasms. This is the first evidence that MSI-H cancers may follow a different pathway to angiogenesis. The low frequency of VEGF expression amongst MSI-H cancers may partially explain why these cancers are less aggressive, with a better overall prognosis. Copyright (C) 1999 John Wiley & Sons, Ltd.
Keyword Pathology
Microsatellite Markers
Colorectal Neoplasms
Vascular Endothelial Growth Factor
Fibroblast Growth Factor
Basic
Protein P53
Angiogenesis Factor
Blood Vessels
Endothelial Growth-factor
Vascular-permeability Factor
Human Colon-cancer
Factor Expression
Gene-expression
Carcinoma Cells
P53
Adenocarcinomas
Tumors
Proliferation
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 10 Jun 2008, 23:48:34 EST