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

Songdong Meng, 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)17361-17365
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number46
DOIs
StatePublished - Nov 14 2006
Externally publishedYes

    Fingerprint

Keywords

  • Amplification
  • Expression
  • Oncogene coamplification

ASJC Scopus subject areas

  • General

Cite this

Meng, S., Tripathy, D., Shete, S., Ashfaq, R., Saboorian, H., Haley, B., Frenkel, E., Euhus, D., Leitch, M., Osborne, C., Clifford, E., Perkins, S., Beitsch, P., Khan, A., Morrison, L., Herlyn, D., Terstappen, L. W. M. M., Lane, N., Wang, J., & Uhr, J. (2006). uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. Proceedings of the National Academy of Sciences of the United States of America, 103(46), 17361-17365. https://doi.org/10.1073/pnas.0608113103