Multichromatic phenotyping of HER receptor coexpression in breast tumor tissue samples using flow cytometry--possibilities and limitations.
The prognostic significance of HER2 expression in human breast carcinomas is beyond dispute nowadays. The HER family of receptor tyrosine kinases comprises four members (HER1/ErbB1/EGFR, HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4) that act in concert via transactivation and consequently compose a functional signaling unit. Besides HER2 overexpression, coexpression of other HER receptors has substantial impact on course of disease and potential therapeutic benefit. This observation is substantiated by numerous preclinical studies and retrospective studies done on patients with breast cancer. Against this background, the quantification of all HER receptor expressions at the same time would significantly extend the information content revealed by routine diagnosis of breast cancer tissues. Moreover, the knowledge of HER receptor coexpression profiles in primary tumor samples could provide the basis to design and develop highly specific antireceptor treatment strategies. Here, we report on a simultaneous flow cytometric detection of all four HER receptors on carcinoma cells isolated from primary breast cancer tissues and separated from nonepithelial cells by cytokeratin staining. Combined with DNA, i.e. ploidy quantification, the approach resulted in a six-parameter assay that could complement the diagnosis of a variety of diseases in which HER receptor expression has a pivotal impact on the degree of malignancy.
Vollmann-Zwerenz
Arabel
A
Institute of Pathology, University of Regensburg, Germany.
Diermeier-Daucher
Simone
S
Wege
Anja Kathrin
AK
Sassen
Andrea
A
Schmidt-Brücken
Elisabeth
E
Hofstaedter
Ferdinand
F
Ortmann
Olaf
O
Nauwelaers
Frans
F
Brockhoff
Gero
G
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013194:Staining and Labeling
D004273:DNA, Neoplasm; D020794:Receptor Protein-Tyrosine Kinases