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Vascular endothelial growth factor, FLT‐1, and FLK‐1 analysis in a pancreatic cancer tissue microarray
Author(s) -
Chung Gina G.,
Yoon Harry H.,
Zerkowski Maciej P.,
Ghosh Sriparna,
Thomas Laurie,
Harigopal Malini,
Charette Lori A.,
Salem Ronald R.,
Camp Robert L.,
Rimm David L.,
Burtness Barbara A.
Publication year - 2006
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21783
Subject(s) - tissue microarray , cytokeratin , pancreatic cancer , vascular endothelial growth factor , immunohistochemistry , pathology , medicine , adenocarcinoma , pancreas , cancer , vascular endothelial growth factor c , oncology , vascular endothelial growth factor a , cancer research , vegf receptors
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.