uPAR and HER-2 Gene Status in Individual Breast Cancer Cells from Blood and Tissues

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. Dr...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2006-11, Vol.103 (46), p.17361-17365
Main Authors: Meng, Songdong, Tripathy, Debu, Shete, Sanjay, Ashfaq, Raheela, Saboorian, Hossein, Haley, Barbara, Frenkel, Eugene, Euhus, David, Leitch, Marilyn, Osborne, Cynthia, Clifford, Edward, Perkins, Steve, Beitsch, Peter, Khan, Amanullah, Morrison, Larry, Herlyn, Dorothee, Terstappen, Leon W. M. M., Lane, Nancy, Wang, Jianqiang, Uhr, Jonathan
Format: Article
Language:English
Subjects:
Antibodies
Biological Sciences
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Cell Line, Tumor
Cell Movement
Epithelial cells
Female
Gene amplification
Gene Amplification - genetics
Gene expression
Gene Expression Regulation, Neoplastic
Genes
Genetic concordance
Humans
Ligands
Oncogenes
Pathology
Receptor, ErbB-2 - genetics
Receptors, Cell Surface - genetics
Receptors, Urokinase Plasminogen Activator
Studies
Tumors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0608113103