通过荧光原位杂交（FISH）检测HER2基因扩增：美国临床肿瘤学会-美国病理学家学会指南与用于乳腺癌国际研究组临床试验入组的FISH评分的比较

HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials.

作者信息

Press Michael F, Sauter Guido, Buyse Marc, Fourmanoir Hélène, Quinaux Emmanuel, Tsao-Wei Denice D, Eiermann Wolfgang, Robert Nicholas, Pienkowski Tadeusz, Crown John, Martin Miguel, Valero Vicente, Mackey John R, Bee Valerie, Ma Yanling, Villalobos Ivonne, Campeau Anaamika, Mirlacher Martina, Lindsay Mary-Ann, Slamon Dennis J

机构信息

Michael F. Press, Denice D. Tsao-Wei, Yanling Ma, Ivonne Villalobos, and Anaamika Campeau, University of Southern California Norris Comprehensive Cancer Center; Dennis J. Slamon, Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA; Nicholas Robert, Virginia Cancer Specialists/US Oncology Research Network, Fairfax, VA; Vicente Valero, The University of Texas MD Anderson Cancer Center, Houston, TX; Guido Sauter and Martina Mirlacher, University of Hamburg, Hamburg; Wolfgang Eiermann, Frauenklinik vom Roten Kreuz, Munich, Germany; Marc Buyse, Hélène Fourmanoir, and Emmanuel Quinaux, International Drug Development Institute, Louvain-la-Neuve, Belgium; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; John Crown, Irish Cooperative Onoclogy Research Group, St Vincent's University Hospital, Dublin, Ireland; Miguel Martin, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain; John R. Mackey, University of Alberta; Mary-Ann Lindsay, Cancer International Research Group/Translational Research in Oncology, Edmonton, Alberta, Canada; and Valerie Bee, Cancer International Research Group/Translational Research in Oncology, Paris, France.

出版信息

J Clin Oncol. 2016 Oct 10;34(29):3518-3528. doi: 10.1200/JCO.2016.66.6693.

DOI:10.1200/JCO.2016.66.6693

PMID:27573653

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5074347/

Abstract

Purpose ASCO and the College of American Pathologists (ASCO-CAP) recently recommended further changes to the evaluation of human epidermal growth factor receptor 2 gene (HER2) amplification by fluorescent in situ hybridization (FISH). We retrospectively assessed the impact of these new guidelines by using annotated Breast Cancer International Research Group (BCIRG) -005, BCIRG-006, and BCIRG-007 clinical trials data for which we have detailed outcomes. Patients and Methods The HER2 FISH status of BCIRG-005/006/007 patients with breast cancers was re-evaluated according to current ASCO-CAP guidelines, which designates five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell: group 1 (in situ hybridization [ISH]-positive): HER2-to-chromosome 17 centromere ratio ≥ 2.0, average HER2 copies ≥ 4.0; group 2 (ISH-positive): ratio ≥ 2.0, copies < 4.0; group 3 (ISH-positive): ratio < 2.0, copies ≥ 6.0; group 4 (ISH-equivocal): ratio < 2.0, copies ≥ 4.0 and < 6.0; and group 5 (ISH-negative): ratio < 2.0, copies < 4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free survival (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio [HR]). Results Among 10,468 patients with breast cancers who were successfully screened for trial entry, 40.8% were in ASCO-CAP ISH group 1, 0.7% in group 2; 0.5% in group 3, 4.1% in group 4, and 53.9% in group 5. Distributions were similar in screened compared with accrued subpopulations. Among accrued patients, FISH group 1 breast cancers were strongly correlated with immunohistochemistry 3+ status (P < .0001), whereas groups 2, 3, 4, and 5 were not; however, groups 2, 4 and, 5 were strongly correlated with immunohistochemistry 0/1+ status (all P < .0001), whereas group 3 was not. Among patients accrued to BCIRG-005, group 4 was not associated with significantly worse DFS or OS compared with group 5. Among patients accrued to BCIRG-006, only group 1 showed a significant benefit from trastuzumab therapy (DFS HR, 0.71; 95% CI, 0.60 to 0.83; P < .0001; OS HR, 0.69; 95% CI, 0.55 to 0.85; P = .0006), whereas group 2 did not. Conclusion Our findings support the original categorizations of HER2 by FISH status in BCIRG/Translational Research in Oncology trials.

摘要

目的美国临床肿瘤学会（ASCO）和美国病理学家学会（ASCO-CAP）最近建议对通过荧光原位杂交（FISH）评估人表皮生长因子受体2基因（HER2）扩增进行进一步更改。我们通过使用注释的乳腺癌国际研究组（BCIRG）-005、BCIRG-006和BCIRG-007临床试验数据进行回顾性评估这些新指南的影响，我们拥有这些试验的详细结果。患者和方法根据当前ASCO-CAP指南对BCIRG-005/006/007乳腺癌患者的HER2 FISH状态进行重新评估，该指南根据HER2 FISH比率和每个肿瘤细胞的平均HER2基因拷贝数指定五个不同组：第1组（原位杂交[ISH]阳性）：HER2与17号染色体着丝粒比率≥2.0，平均HER2拷贝数≥4.0；第2组（ISH阳性）：比率≥2.0，拷贝数<4.0；第3组（ISH阳性）：比率<2.0，拷贝数≥6.0；第4组（ISH可疑）：比率<2.0，拷贝数≥4.0且<6.0；第5组（ISH阴性）：比率<2.0，拷贝数<4.0。我们评估了与HER2蛋白的相关性、通过无病生存期（DFS）和总生存期（OS）评估的临床结果以及从曲妥珠单抗治疗中获得的益处（风险比[HR]）。结果在成功筛选进入试验的10468例乳腺癌患者中，40.8%属于ASCO-CAP ISH第1组，0.7%属于第2组；0.5%属于第3组，4.1%属于第4组，53.9%属于第5组。与入组亚组相比，筛选人群中的分布相似。在入组患者中，FISH第1组乳腺癌与免疫组化3+状态密切相关（P<.0001），而第2、3、4和5组则不然；然而，第2、4和5组与免疫组化0/1+状态密切相关（所有P<.0001），而第3组则不然。在BCIRG-005入组的患者中，与第5组相比，第4组的DFS或OS并无显著更差。在BCIRG-006入组的患者中，只有第1组从曲妥珠单抗治疗中显示出显著益处（DFS HR，0.71；95%CI，0.60至0.83；P<.0001；OS HR，0.69；95%CI，0.55至0.85；P=.0006），而第2组则没有。结论我们的研究结果支持BCIRG/肿瘤转化研究试验中通过FISH状态对HER2进行的原始分类。