Register for email alerts and news feeds:
This journal | BMJ Group
rss
Journal of Clinical Pathology 2004;57:504-512; doi:10.1136/jcp.2003.012963
Copyright © 2004 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists.
Journal of Clinical Pathology 2004;57:504-512
© 2004 BMJ Publishing Group Ltd & Association of Clinical Pathologists

ORIGINAL ARTICLE

Expression of vascular endothelial growth factor, hypoxia inducible factor 1{alpha}, and carbonic anhydrase IX in human tumours

A M Jubb1, T Q Pham1, A M Hanby2, G D Frantz1, F V Peale1, T D Wu3, H W Koeppen1 and K J Hillan1

1 Department of Pathology, Genentech Inc, South San Francisco, CA94080, USA
2 Department of Academic Unit of Pathology, University of Leeds, Leeds, UK
3 Department of Bioinformatics, Genentech Inc

Correspondence to:
Correspondence to:
A Jubb
Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA; adrianj{at}gene.com

Aims: To measure vascular endothelial growth factor (VEGF-A) mRNA in a large, diverse cohort of tumours and to investigate whether VEGF-A expression is associated with markers of hypoxia, including hypoxia inducible factor 1{alpha} (HIF-1{alpha}) and carbonic anhydrase IX (CA9).

Methods: The expression of VEGF-A and CA9 was assessed in 5067 fresh frozen human tissue samples and 238 cell lines by DNA microarray analysis. In addition, tissue microarrays were constructed from 388 malignancies to investigate the expression of VEGF-A and HIF-1{alpha} by in situ hybridisation and immunohistochemistry, respectively.

Results: VEGF-A was significantly upregulated in primary malignancies of the breast, cervix, colon and rectum, oesophagus, head and neck, kidney, ovary, skin, urinary system, and white blood cells by DNA microarray analysis. However, VEGF-A expression only correlated with CA9 expression in renal tissues. In the tissue microarrays, HIF-1{alpha} positive cores showed a significant increase in VEGF-A expression in lung, ovary, soft tissue, and thyroid malignancies.

Conclusions: The expression of VEGF-A is upregulated in a large proportion of human malignancies, and may be associated with markers of hypoxia. VEGF-A expression can be induced in the absence of hypoxia and hypoxia does not always provoke VEGF-A upregulation in tumours.

Keywords: vascular endothelial growth factor; hypoxia inducible factor one alpha; carbonic anhydrase IX; angiogenesis; neoplasia

Abbreviations: CA9, carbonic anhydrase IX; CHO, Chinese hamster ovary; H&E, haematoxylin and eosin; HIF-1{alpha}, hypoxia inducible factor 1{alpha}; IHC, immunohistochemistry; ISH, in situ hybridisation; PCR, polymerase chain reaction; TMA, tissue microarray; VEGF-A, vascular endothelial growth factor A; VHL, von Hippel-Lindau


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

This article has been cited by other articles:

  • SIEMANN, D. W., NORRIS, C. M., RYAN, A., SHI, W. (2009). Impact of Tumor Cell VEGF Expression on the In Vivo Efficacy of Vandetanib (ZACTIMATM; ZD6474). Anticancer Res 29: 1987-1992 [Abstract] [Full Text]  
  • Wiseman, S. M., Melck, A., Masoudi, H., Ghaidi, F., Goldstein, L., Gown, A., Jones, S. J. M., Griffith, O. L. (2008). Molecular Phenotyping of Thyroid Tumors Identifies a Marker Panel for Differentiated Thyroid Cancer Diagnosis. Ann. Surg. Oncol. 15: 2811-2826 [Abstract] [Full Text]  
  • Jubb, A. M., Hurwitz, H. I., Bai, W., Holmgren, E. B., Tobin, P., Guerrero, A. S., Kabbinavar, F., Holden, S. N., Novotny, W. F., Frantz, G. D., Hillan, K. J., Koeppen, H. (2006). Impact of Vascular Endothelial Growth Factor-A Expression, Thrombospondin-2 Expression, and Microvessel Density on the Treatment Effect of Bevacizumab in Metastatic Colorectal Cancer. JCO 24: 217-227 [Abstract] [Full Text]  
  • Jubb, A, Hillan, K (2005). Expression of HIF-1{alpha} in human tumours. J. Clin. Pathol. 58: 1344-1344 [Full Text]  
  • Gray, D., Jubb, A. M., Hogue, D., Dowd, P., Kljavin, N., Yi, S., Bai, W., Frantz, G., Zhang, Z., Koeppen, H., de Sauvage, F. J., Davis, D. P. (2005). Maternal Embryonic Leucine Zipper Kinase/Murine Protein Serine-Threonine Kinase 38 Is a Promising Therapeutic Target for Multiple Cancers. Cancer Res. 65: 9751-9761 [Abstract] [Full Text]  
  • Ince, W. L., Jubb, A. M., Holden, S. N., Holmgren, E. B., Tobin, P., Sridhar, M., Hurwitz, H. I., Kabbinavar, F., Novotny, W. F., Hillan, K. J., Koeppen, H. (2005). Association of k-ras, b-raf, and p53 Status With the Treatment Effect of Bevacizumab. JNCI J Natl Cancer Inst 97: 981-989 [Abstract] [Full Text]  
  • van Diest, P J, Vleugel, M M, van der Wall, E, Currie, M J, Hanrahan, V, Gunningham, S P, Morrin, H R, Frampton, C, Han, C, Robinson, B A, Fox, S B (2005). Expression of HIF-1{alpha} in human tumours. J. Clin. Pathol. 58: 335-336 [Full Text]  
  • Vleugel, M M, Greijer, A E, Shvarts, A, van der Groep, P, van Berkel, M, Aarbodem, Y, van Tinteren, H, Harris, A L, van Diest, P J, van der Wall, E (2005). Differential prognostic impact of hypoxia induced and diffuse HIF-1{alpha} expression in invasive breast cancer. J. Clin. Pathol. 58: 172-177 [Abstract] [Full Text]  
  • Lam, J. S., Belldegrun, A. S., Figlin, R. A. (2004). Tissue Array-Based Predictions of Pathobiology, Prognosis, and Response to Treatment for Renal Cell Carcinoma Therapy. Clin. Cancer Res. 10: 6304S-6309S [Abstract] [Full Text]  
  • Fox, S. B., Braganca, J., Turley, H., Campo, L., Han, C., Gatter, K. C., Bhattacharya, S., Harris, A. L. (2004). CITED4 Inhibits Hypoxia-Activated Transcription in Cancer Cells, and Its Cytoplasmic Location in Breast Cancer Is Associated with Elevated Expression of Tumor Cell Hypoxia-Inducible Factor 1{alpha}. Cancer Res. 64: 6075-6081 [Abstract] [Full Text]  

This Article

Services
Citing Articles
Google Scholar
PubMed
Topic Collections
Bookmark with

Register for free content

The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.

Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.

Pathology jobs

Pathology jobs