PMID- 9256133 OWN - NLM STAT- MEDLINE DCOM- 19970908 LR - 20220420 IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 15 IP - 8 DP - 1997 Aug TI - HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas. PG - 2894-904 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 HER-2/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. FAU - Press, M F AU - Press MF AD - Norris Comprehensive Cancer Center and Department of Pathology, University of Southern California School of Medicine, Los Angeles, CA 90033, USA. villalob@hsc.usc.edu FAU - Bernstein, L AU - Bernstein L FAU - Thomas, P A AU - Thomas PA FAU - Meisner, L F AU - Meisner LF FAU - Zhou, J Y AU - Zhou JY FAU - Ma, Y AU - Ma Y FAU - Hung, G AU - Hung G FAU - Robinson, R A AU - Robinson RA FAU - Harris, C AU - Harris C FAU - El-Naggar, A AU - El-Naggar A FAU - Slamon, D J AU - Slamon DJ FAU - Phillips, R N AU - Phillips RN FAU - Ross, J S AU - Ross JS FAU - Wolman, S R AU - Wolman SR FAU - Flom, K J AU - Flom KJ LA - eng GR - CA48780/CA/NCI NIH HHS/United States GR - CA58197/CA/NCI NIH HHS/United States GR - N01-HD-3-3175/HD/NICHD NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Aged MH - Biomarkers, Tumor/genetics MH - Breast Neoplasms/genetics/mortality/*pathology MH - Female MH - *Gene Amplification MH - Humans MH - Immunoblotting MH - In Situ Hybridization, Fluorescence MH - Lymphatic Metastasis MH - Middle Aged MH - Neoplasm Metastasis MH - Neoplasm Recurrence, Local MH - Prognosis MH - Receptor, ErbB-2/*genetics MH - Sensitivity and Specificity MH - Survival Rate EDAT- 1997/08/01 00:00 MHDA- 1997/08/01 00:01 CRDT- 1997/08/01 00:00 PHST- 1997/08/01 00:00 [pubmed] PHST- 1997/08/01 00:01 [medline] PHST- 1997/08/01 00:00 [entrez] AID - 10.1200/JCO.1997.15.8.2894 [doi] PST - ppublish SO - J Clin Oncol. 1997 Aug;15(8):2894-904. doi: 10.1200/JCO.1997.15.8.2894.