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

Gina G. Chung, Harry H Yoon, Maciej P. Zerkowski, Sriparna Ghosh, Laurie Thomas, Malini Harigopal, Lori A. Charette, Ronald R. Salem, Robert L. Camp, David L. Rimm, Barbara A. Burtness

Research output: Contribution to journalArticle

59 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1677-1684
Number of pages8
JournalCancer
Volume106
Issue number8
DOIs
StatePublished - May 15 2006
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor
Keratins
Neoplasms
Survival
Antibodies
Kaplan-Meier Estimate
Masks
Pancreas
Adenocarcinoma
Multivariate Analysis
Immunohistochemistry
Pathology
Staining and Labeling
Antigens
Membranes
Proteins

Keywords

  • Angiogenesis
  • FLT-1
  • Quantitative image analysis
  • Tissue microarray

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Chung, G. G., Yoon, H. H., Zerkowski, M. P., Ghosh, S., Thomas, L., Harigopal, M., ... Burtness, B. A. (2006). Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray. Cancer, 106(8), 1677-1684. https://doi.org/10.1002/cncr.21783

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

In: Cancer, Vol. 106, No. 8, 15.05.2006, p. 1677-1684.

Research output: Contribution to journalArticle

Chung, GG, Yoon, HH, Zerkowski, MP, Ghosh, S, Thomas, L, Harigopal, M, Charette, LA, Salem, RR, Camp, RL, Rimm, DL & Burtness, BA 2006, 'Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray', Cancer, vol. 106, no. 8, pp. 1677-1684. https://doi.org/10.1002/cncr.21783
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. / Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray. In: Cancer. 2006 ; Vol. 106, No. 8. pp. 1677-1684.
@article{6f30fabc750746d3befb46ecda9ca755,
title = "Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray",
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.",
keywords = "Angiogenesis, FLT-1, Quantitative image analysis, Tissue microarray",
author = "Chung, {Gina G.} and Yoon, {Harry H} and Zerkowski, {Maciej P.} and Sriparna Ghosh and Laurie Thomas and Malini Harigopal and Charette, {Lori A.} and Salem, {Ronald R.} and Camp, {Robert L.} and Rimm, {David L.} and Burtness, {Barbara A.}",
year = "2006",
month = "5",
day = "15",
doi = "10.1002/cncr.21783",
language = "English (US)",
volume = "106",
pages = "1677--1684",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "8",

}

TY - JOUR

T1 - Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray

AU - Chung, Gina G.

AU - Yoon, Harry H

AU - Zerkowski, Maciej P.

AU - Ghosh, Sriparna

AU - Thomas, Laurie

AU - Harigopal, Malini

AU - Charette, Lori A.

AU - Salem, Ronald R.

AU - Camp, Robert L.

AU - Rimm, David L.

AU - Burtness, Barbara A.

PY - 2006/5/15

Y1 - 2006/5/15

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - FLT-1

KW - Quantitative image analysis

KW - Tissue microarray

UR - http://www.scopus.com/inward/record.url?scp=33646021965&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646021965&partnerID=8YFLogxK

U2 - 10.1002/cncr.21783

DO - 10.1002/cncr.21783

M3 - Article

C2 - 16532435

AN - SCOPUS:33646021965

VL - 106

SP - 1677

EP - 1684

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 8

ER -