PLASMA-MEMBRANE PHOSPHOTYROSINE, HER2-NEU, AND EPIDERMAL GROWTH-FACTOR RECEPTOR IN HUMAN BREAST-CANCER - A COMPARATIVE-STUDY

Experimental therapeutic regimens for breast cancer include strategies to block the activity of specific oncogenes. Because oncogenesis is a multistep process, specific oncogenes may drive tumor production at o ne stage yet not function in another. Since the effectiveness of thera py targeted against oncogenes depends on their function in the tumor, correlation of oncogene function to specific stages of tumor developme nt has therapeutic implications. Among the oncogenes known to be impor tant in breast cancer production are two cell surface growth factor re ceptors, epidermal growth factor receptor (EGFR) and Her2-NEU (NEU). T hese proteins are receptor tyrosine kinases that autophosphorylate spe cific tyrosine residues on activation. The oncogenic potential of thes e receptors depends on this autophosphorylation. We examined 86 primar y formalin-fixed, paraffin-embedded breast tumors for overexpression o f EGFR and NEU and correlated our findings with the presence of cell s urface phosphotyrosine as an indicator of tyrosine kinase activity at the plasma membrane. Our data indicate that only 34% of tumors that ov erexpress EGFR or NEU show plasma membrane phosphotyrosine, indicating that in the majority of these tumors, the overexpressed oncogene may not be active at this stage.