HER-2 NEU GENE AMPLIFICATION CHARACTERIZED BY FLUORESCENCE IN-SITU HYBRIDIZATION - POOR-PROGNOSIS IN NODE-NEGATIVE BREAST CARCINOMAS/

Purpose: The HER-2/neu gene codes for a membrane receptor protein that is homologous, but distinct from the epidermal growth factor receptor . This investigation was performed to validate fluorescence in situ hy bridization (FISH) as a sensitive and specific method for assessing HE R-2/neu gene amplification in archival tissue and to test whether this alteration is associated with poor prognosis, Materials and Methods: HER-2/neu gene amplification was determined by FISH in 140 archival br east cancers, previously characterized for gene amplification by South ern hybridisation or dot-blot hybridization, and for gene expression b y Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node-negative breast cancers was assessed fo r amplification by FISH to determine the utility of HER-2/neu gene amp lification. Results: Relative to solid-matrix blotting procedures, FIS H analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers, Among patients treat ed by surgery only, the relative risks (relative hazard) of early recu rrence (recurrent disease within 24 months of diagnosis), recurrent di sease (at any time), and disease-related death were statistically sign ificantly associated with amplification, The prognostic information co ntributed by HER-2/neu amplification was independent of the other mark ers studied, Conclusion: FISH was an alternative technique for determi ning gene amplification and had some distinct advantages over Southern hybridization, Our results demonstrate that HER-2/neu gene amplificat ion in the absence of adjuvant therapy is an independent predictor of poor clinical outcome and is a stronger discriminant than tumor size. Women with small tumors that had gene amplification were at increased risk of recurrence and disease-related death. (C) 1997 by American Soc iety of Clinical Oncology.