HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.
HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.
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通过荧光原位杂交进行 HER-2/neu 基因扩增，可以对淋巴结阴性乳腺癌进行风险组评估。
DOI：
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发表时间：
1999
影响因子：
5.2
通讯作者：
M. Schmitt
中科院分区：
文献类型：
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作者：
N. Harbeck;J. Ross;S. Yurdseven;P. Dettmar;M. Pölcher;W. Kuhn;K. Ulm;H. Graeff;M. Schmitt
在112例淋巴结阴性的乳腺癌患者中，我们比较了荧光原位杂交(FISH)检测的HER-2/neu基因扩增(AMP)和免疫组织化学(IHC)检测的HER-2/neu蛋白过表达(EXP)与传统预后因素(肿瘤大小、分级、激素受体状态、绝经状况)以及肿瘤侵袭标志物尿激酶型纤溶酶原激活物(UPA)及其抑制物(PAI-1)的影响。分析时仍活着的患者的中位随访期为7年。在福尔马林固定石蜡包埋的平行切片上进行自动FISH和IHC。FISH法检测HER-2/neu AMP的阳性率为31%，IHC法检测HER-2/neu EXP的阳性率为41%。13%的肿瘤同时存在AMP和EXP。在所有分析的病例中，FISH和IHC结果有56%是一致的。在单因素分析中，HER-2/neu AMP显著预测无病(DFS)和总生存期(OS)。HER-2/neu EXP仅对OS有意义。在对所有分析的预后因素进行多因素分析中，HER-2/neu AMP是DFS和OS的唯一独立预测因素。CART分析显示，HER-2/neu AMP与uPA/PAI-1联合应用可在7年的中位随访期内提供最佳风险组评估：uPA和PAI-1水平均较低且无HER-2/neu AMP的患者复发率(4.6%)显著低于其余患者(32%)。综上所述，FISH检测的HER-2/neu基因AMP比IHC检测的HER-2/neu蛋白EXP能更准确地进行风险组评估。将FISH检测的HER-2/neu基因状态与肿瘤侵袭标记物uPA和PAI-1水平相结合，可改善临床相关的风险组评估。HER-2/neu AMP对OS的显著影响除了其预测预后的力量外，可能还反映了其预测系统治疗耐药性的能力。
In a collective of 112 node-negative breast cancer patients, we compared the prognostic impact of HER-2/neu gene amplification (AMP) determined by fluorescence in situ hybridization (FISH) and HER-2/neu protein overexpression (EXP) measured by immunohistochemistry (IHC) with traditional prognostic factors (tumor size, grade, steroid hormone receptor status, menopausal status) and tumor invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 determined by enzyme immunoassay (ELISA). Median follow-up in patients still alive at time of analysis was 7 years. Automated FISH and IHC were performed on parallel-cut formalin-fixed paraffin-embedded tissue sections. HER-2/neu AMP was detected by FISH in 31% and HER-2/neu EXP was measured by IHC in 41% of the cases. In 13% of the tumors, both AMP and EXP were found. FISH and IHC results were concordant in 56% of all analyzed cases. In univariate analysis, HER-2/neu AMP significantly predicted both disease-free (DFS) and overall survival (OS). HER-2/neu EXP was significant for OS, only. In multivariate analysis of all analyzed prognostic factors, HER-2/neu AMP was the only independent predictive factor for both DFS and OS. CART analysis revealed that HER-2/neu AMP together with the combination uPA/PAI-1 allowed optimal risk-group assessment after a 7-year median follow-up: patients with low levels of both uPA and PAI-1 and no HER-2/neu AMP had a significantly lower relapse rate (4.6%) than the remaining patients (32%). In conclusion, HER-2/neu gene AMP determined by FISH allowed a more accurate risk-group assessment than HER-2/neu protein EXP measured by IHC. Combining the HER-2/neu gene status measured by FISH with levels of tumor invasion markers uPA and PAI-1 improves clinically relevant risk-group assessment. In addition to its prognostic strength, the significant impact of HER-2/neu AMP on OS may reflect its ability to predict resistance to systemic therapy.