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

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 abse...

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Bibliographic Details
Published in:	The Journal of pathology Vol. 189; no. 3; pp. 319 - 325
Main Authors:	Wynter, Coral V. A., Simms, Lisa A., Buttenshaw, Ron L., Biden, Kelli G., Young, Joanne, Leggett, Barbara A., Conrad, Rod J., Schoch, Estelle M., Jass, Jeremy R., Praga Pillay, S.
Format:	Journal Article
Language:	English
Published:	Chichester, UK John Wiley & Sons, Ltd 01-11-1999 Wiley
Subjects:	Adenocarcinoma - blood supply Adenocarcinoma - genetics Adenocarcinoma - metabolism angiogenesis factor basic Biological and medical sciences blood vessels Blotting, Western colorectal neoplasms Colorectal Neoplasms - blood supply Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism DNA, Neoplasm - genetics Endothelial Growth Factors - metabolism fibroblast growth factor Fibroblast Growth Factor 2 - metabolism Gastroenterology. Liver. Pancreas. Abdomen Humans Lymphokines - metabolism Medical sciences microsatellite markers Microsatellite Repeats - genetics Neoplasm Proteins - metabolism Neovascularization, Pathologic - pathology protein p53 Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumor Suppressor Protein p53 - metabolism Tumors vascular endothelial growth factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Human Immunohistochemistry Fibroblast growth factor Rectal disease Carcinoma Prognosis Cytokine Malignant tumor Carcinogenesis Colonic disease Polymerase chain reaction Pathology Angiogenesis Vascular endothelium growth factor Polypeptide Microsatellite DNA Rectum Immunoblotting assay Digestive diseases Intestinal disease Instability Colon Molecular biology Growth factor
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Summary:	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 © 1999 John Wiley & Sons, Ltd.
Bibliography:	ark:/67375/WNG-N2GBTM5V-D ArticleID:PATH436 istex:DEAC4BBC7610F72466357EDA43B3BE3B30D2EA27 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-3417 1096-9896
DOI:	10.1002/(SICI)1096-9896(199911)189:3<319::AID-PATH436>3.0.CO;2-2