FUNCTIONAL ASSAY FOR HER-2 NEU DEMONSTRATES ACTIVE SIGNALING IN A MINORITY OF HER-2/NEU-OVEREXPRESSING INVASIVE HUMAN BREAST-TUMORS/

Overexpression of HER-2/neu in human breast carcinomas correlates with poor prognosis. although irs strength as a prognostic indicator varie s widely in different reports. Variability may be due to active signal ling by HER-2/neu in a subset of the rumours in which it is overexpres sed. To study this hypothesis, we have developed an activation state-s pecific anti-HER-2/neu monoclonal antibody. In this report. we use thi s antibody to analyse the signalling status of HER-2/neu in a large se ries of invasive breast carcinomas. Overexpression of HER-2/neu was de tected in 9% of 223 cases. Of the cases demonstrating overexpression, active signalling by HER-2/neu was detected in only 35%. The clinicopa thological characteristics of these cases are described. This function al assay is predicted to improve the utility of HER-2/neu as a prognos tic indicator.