title: uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues.
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.
authors.affiliation: Cancer Immunobiology Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Songdong
authors.initials: S
authors.lastname: Meng
authors.forename: Debu
authors.initials: D
authors.lastname: Tripathy
authors.forename: Sanjay
authors.initials: S
authors.lastname: Shete
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Hossein
authors.initials: H
authors.lastname: Saboorian
authors.forename: Barbara
authors.initials: B
authors.lastname: Haley
authors.forename: Eugene
authors.initials: E
authors.lastname: Frenkel
authors.forename: David
authors.initials: D
authors.lastname: Euhus
authors.forename: Marilyn
authors.initials: M
authors.lastname: Leitch
authors.forename: Cynthia
authors.initials: C
authors.lastname: Osborne
authors.forename: Edward
authors.initials: E
authors.lastname: Clifford
authors.forename: Steve
authors.initials: S
authors.lastname: Perkins
authors.forename: Peter
authors.initials: P
authors.lastname: Beitsch
authors.forename: Amanullah
authors.initials: A
authors.lastname: Khan
authors.forename: Larry
authors.initials: L
authors.lastname: Morrison
authors.forename: Dorothee
authors.initials: D
authors.lastname: Herlyn
authors.forename: Leon W M M
authors.initials: LW
authors.lastname: Terstappen
authors.forename: Nancy
authors.initials: N
authors.lastname: Lane
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Uhr
mesh_terms: D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C524898:PLAUR protein, human