HER-2/neu gene amplification characterized by fluorescence in situ hybridization: Poor prognosis in node-negative breast carcinomas
HER-2/neu gene amplification characterized by fluorescence in situ hybridization: Poor prognosis in node-negative breast carcinomas
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DOI：
10.1200/jco.1997.15.8.2894
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发表时间：
1997-08-01
影响因子：
45.3
通讯作者：
Flom, KJ
中科院分区：
文献类型：
--
作者：
Press, MF;Bernstein, L;Flom, KJ
目的：HER-2/neu基因编码的膜受体蛋白是同源的，但不同于表皮生长因子受体。本研究旨在验证荧光原位杂交（FISH）作为评估档案组织中HER-2/neu基因扩增的敏感和特异性方法，并测试这种改变是否与预后不良有关。HER-2/neu基因扩增在140例乳腺癌档案中通过FISH检测，先前的特征是通过Southern杂交或点印迹杂交进行基因扩增，通过Northern杂交、Western免疫印迹或免疫组织化学进行基因表达。通过FISH对324例淋巴结阴性乳腺癌的单独队列进行扩增评估，以确定HER-2/neu基因扩增的效用。结果:相对于固体基质印迹法，HER-2/neu基因扩增的FISH分析显示，在140例乳腺癌中，HER-2/neu基因扩增的敏感性为98%，特异性为100%。在仅接受手术治疗的患者中，早期复发（诊断后24个月内复发）、复发（任何时间）和疾病相关死亡的相对风险（相对危险）与扩增有统计学显著相关。结论：FISH是一种确定基因扩增的替代技术，与Southern杂交相比有一些明显的优势。我们的研究结果表明，在没有辅助治疗的情况下，HER-2/neu基因扩增是临床预后不良的独立预测指标，比肿瘤大小具有更强的判别性。患有基因扩增的小肿瘤的妇女复发和疾病相关死亡的风险增加。(C) 1997年由美国临床肿瘤学会。
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 hybridisation 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. (C) 1997 by American Society of Clinical Oncology.