Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Cancer, 2006-04, Vol.106 (8), p.1677-1684

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2006

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. To compare the in situ expression of vascular endothelial growth factor (VEGF) and its primary receptors VEGF receptor 1 (FLT‐1) and VEGF receptor 2 (FLK‐1) on a pancreatic cancer tissue microarray (TMA), the authors used their own series of algorithms (AQUA). Using TMA and the AQUA technologies as a platform, the results showed that VEGF, FLT‐1, and FLK‐1 were expressed variably in pancreatic adenocarcinomas and that FLT‐1 was correlated significantly with disease stage and survival.