Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray

Authors

  • Gina G. Chung M.D.,

    Corresponding author
    1. Yale Cancer Center and Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut
    • Section of Medical Oncology, Yale Cancer Center 333 Cedar Street, P.O. Box 208032, New Haven, CT 06520
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    • Fax: (203) 785-3788

  • Harry H. Yoon M.D.,

    1. Yale Cancer Center and Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut
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  • Maciej P. Zerkowski,

    1. Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
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  • Sriparna Ghosh Ph.D,

    1. Yale Cancer Center and Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut
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  • Laurie Thomas,

    1. Yale Cancer Center and Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut
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  • Malini Harigopal M.D.,

    1. Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
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  • Lori A. Charette,

    1. Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
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  • Ronald R. Salem M.D.,

    1. Department of Surgery, Yale University School of Medicine, New Haven, Connecticut
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  • Robert L. Camp M.D., Ph.D,

    1. Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
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    • Robert Camp and David L. Rimm are stock holders, scientific founders, and consultants to HistoRX, a private corporation to which Yale University has given exclusive right to produce and distribute the software and technologies embedded in AQUA. Yale University retains patent rights for the AQUA technology.

  • David L. Rimm M.D., Ph.D,

    1. Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
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    • Robert Camp and David L. Rimm are stock holders, scientific founders, and consultants to HistoRX, a private corporation to which Yale University has given exclusive right to produce and distribute the software and technologies embedded in AQUA. Yale University retains patent rights for the AQUA technology.

  • Barbara A. Burtness M.D.

    1. Yale Cancer Center and Department of Internal Medicine, Section of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut
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  • Presented as a poster at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium, Hollywood, Florida, January 27-29, 2005.

Abstract

BACKGROUND

Measures of vascular endothelial growth factor (VEGF) expression in pancreatic cancer typically have been qualitative or semiquantitative. The objective of this study was to use a series of algorithms called AQUA that quantitatively assesses protein expression on tissue microarrays (TMAs) to compare in situ expression of VEGF and its primary receptors, VEGF receptor 1 (FLT-1) and VEGF receptor 1 (FLK-1), on a pancreatic cancer TMA.

METHODS

TMAs were constructed by arraying 1.5-mm cores from 76 samples of pancreatic adenocarcinoma (1996-2002) that were obtained from the archives of the Yale Department of Pathology. The staining for AQUA was similar to standard immunohistochemistry and involved antigen retrieval and the application of primary antibodies, but with epifluorescence detection. Slides were counterstained with 4′,6-diamidino-2-phenylindole for nuclear visualization and cytokeratin for membrane visualization. The primary antibodies used were VEGF, FLT-1, FLK-1, and cytokeratin.

RESULTS

Disease stage was highly prognostic for outcome, as expected. Total amounts of VEGF and its receptors were assessed within the tumor mask and were divided into quartiles. Kaplan–Meier survival curves showed that VEGF and FLK-1 were not associated clearly with outcome. However, the expression of FLT-1 was correlated significantly, and the patients who had tumors with the lowest expression FLT-1 levels had the worst survival (P = .0038). In multivariate analysis, FLT-1 expression was an independent prognostic factor for overall survival (P = .0044).

CONCLUSIONS

VEGF and its 2 principal receptors were expressed to varying degrees in tumors of the pancreas. A significant association was found between low expression of FLT-1 and both poor prognosis and advanced stage, suggesting that tumor expression of this VEGF receptor is a marker of less aggressive disease. Cancer 2006. © 2006 American Cancer Society.

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