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. 2006 Nov 14;103(46):17361-5.
doi: 10.1073/pnas.0608113103. Epub 2006 Nov 1.

uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues

Songdong Meng  1 , Debu Tripathy, Sanjay Shete, Raheela Ashfaq, Hossein Saboorian, Barbara Haley, Eugene Frenkel, David Euhus, Marilyn Leitch, Cynthia Osborne, Edward Clifford, Steve Perkins, Peter Beitsch, Amanullah Khan, Larry Morrison, Dorothee Herlyn, Leon W M M Terstappen, Nancy Lane, Jianqiang Wang, Jonathan Uhr
Affiliations

uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues

Songdong Meng et al. Proc Natl Acad Sci U S A. .

Abstract

Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for coamplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively.

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Conflict of interest statement

Conflict of interest statement: J.U. holds stock in Immunicon Corporation.

Figures

Fig. 1.
Fig. 1.
Correlation of HER-2 expression and gene amplification in CTCs. (Left) Representative CTCs: nucleus (blue); cytokeratin IF (green); HER-2 IF (red) (overlap of red/green is yellow). (Center) The same cells: nucleus (blue); HER-2 (red). (Right) FISH analysis: HER-2 copies (spectrum orange); CEP 17 copies (spectrum green). HER-2 expression, 1–3+, and HER-2 copy number/CEP17 copy number are shown at right.
Fig. 2.
Fig. 2.
Correlation of uPAR expression and gene amplification in CTCs. (Left) Representative CTCs. (Center) The same cells: nucleus (blue); uPAR (orange). (Right) FISH analysis: uPAR copies (spectrum orange); chr 19 copies (spectrum green); uPAR expression, 1–3+, and uPAR copy number/chr 19 copy number are shown at right.
Fig. 3.
Fig. 3.
Theoretical division of CTCs into subsets with different degrees of amplification for two oncogenes (A and B).
See this image and copyright information in PMC

Comment in

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