TY - JOUR
T1 - HER-2/neu gene amplification characterized by fluorescence in situ hybridization
T2 - Poor prognosis in node-negative breast carcinomas
AU - Press, Michael F.
AU - Bernstein, Leslie
AU - Thomas, Patricia A.
AU - Meisner, Lorraine F.
AU - Zhou, Jian Yuan
AU - Ma, Yanling
AU - Hung, Gene
AU - Robinson, Robert A.
AU - Harris, Charles
AU - El-Naggar, Adel
AU - Slamon, Dennis J.
AU - Phillips, Richard N.
AU - Ross, Jeffrey S.
AU - Wolman, Sandra R.
AU - Flom, Kerry J.
PY - 1997/8
Y1 - 1997/8
N2 - 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 hybridization (FISH) as a sensitive and specific method for assessing HER-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 breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node- negative breast cancers was assessed for amplification by FISH to determine the utility of HER-2/neu gene amplification. Results: Relative to solid- matrix blotting procedures, FISH analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers. Among patients treated by surgery only, the relative risks (relative hazard) of early recurrence (recurrent disease within 24 months of diagnosis), recurrent disease (at any time), and disease-related death were statistically significantly associated with amplification. The prognostic information contributed by HER2/neu amplification was independent of the other markers studied. Conclusion: FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification 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.
AB - 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 hybridization (FISH) as a sensitive and specific method for assessing HER-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 breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node- negative breast cancers was assessed for amplification by FISH to determine the utility of HER-2/neu gene amplification. Results: Relative to solid- matrix blotting procedures, FISH analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers. Among patients treated by surgery only, the relative risks (relative hazard) of early recurrence (recurrent disease within 24 months of diagnosis), recurrent disease (at any time), and disease-related death were statistically significantly associated with amplification. The prognostic information contributed by HER2/neu amplification was independent of the other markers studied. Conclusion: FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification 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.
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U2 - 10.1200/JCO.1997.15.8.2894
DO - 10.1200/JCO.1997.15.8.2894
M3 - Article
C2 - 9256133
AN - SCOPUS:18244422222
SN - 0732-183X
VL - 15
SP - 2894
EP - 2904
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 8
ER -