Multisite phosphotyping of the ErbB-2 oncoprotein in human breast cancer.
BACKGROUND
Overexpression of the ErbB-2 (HER2/neu) receptor tyrosine kinase is one of the most common molecular changes in human cancer, but the functional significance of this phenotype remains uncertain.


RESULTS
Using phosphorylation-specific antibodies recognizing different ErbB-2 functional states, we assessed the phosphorylation status of ErbB-2 in 102 human breast cancer specimens. Quantitative ErbB-2 immunoblotting intensity correlated directly with that of immunohistochemistry (r = 0.84). Widely varying phosphorylation profiles were evident in 65 ErbB-2-positive carcinomas, suggesting different ErbB-2 functions in different tumors. In a subset of patients for whom clinical data were obtainable, mortality trends were strongly associated with the quantitative signal intensities of ErbB-2 phosphoantibodies (P < or =.02), but not with those of conventional antibodies to ErbB-2 (P = .147), epidermal growth factor receptor (P = .44), or phosphotyrosine (P = .94).


CONCLUSIONS
Although requiring corroboration in larger prospective clinical studies, these findings suggest that immunophenotyping using phosphorylation-specific antibodies may enable more accurate prediction of cancer behavior than is currently obtainable using conventional reagents.
Division of Investigative Sciences, Imperial College School of Medicine, London, UK.
X
X
Ouyang
T
T
Gulliford
G C
GC
Huang
C
C
Harper-Wynne
S
S
Shousha
R J
RJ
Epstein
D016475:3T3 Cells; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001666:Binding Sites, Antibody; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010748:Phosphopeptides / Q000008:administration & dosage / Q000276:immunology; D010766:Phosphorylation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D012189:Retrospective Studies; D014407:Tumor Cells, Cultured
D000906:Antibodies; D007527:Isoenzymes; D010748:Phosphopeptides; D018719:Erb-b2 Receptor Tyrosine Kinases