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. 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.
Meng
Songdong
S
Cancer Immunobiology Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Tripathy
Debu
D
Shete
Sanjay
S
Ashfaq
Raheela
R
Saboorian
Hossein
H
Haley
Barbara
B
Frenkel
Eugene
E
Euhus
David
D
Leitch
Marilyn
M
Osborne
Cynthia
C
Clifford
Edward
E
Perkins
Steve
S
Beitsch
Peter
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Khan
Amanullah
A
Morrison
Larry
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Herlyn
Dorothee
D
Terstappen
Leon W M M
LW
Lane
Nancy
N
Wang
Jianqiang
J
Uhr
Jonathan
J
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
D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C524898:PLAUR protein, human