Human Epidermal Growth Factor Receptor 2 Assessment in a Case-Control Study: Comparison of Fluorescence In Situ Hybridization and Quantitative Reverse Transcription Polymerase Chain Reaction Performed by Central Laboratories
Human Epidermal Growth Factor Receptor 2 Assessment in a Case-Control Study: Comparison of Fluorescence In Situ Hybridization and Quantitative Reverse Transcription Polymerase Chain Reaction Performed by Central Laboratories
复制标题
DOI：
10.1200/jco.2009.24.8211
复制
发表时间：
2010-10-01
影响因子：
45.3
通讯作者：
Habel, Laurel A.
中科院分区：
文献类型：
--
作者：
Baehner, Frederick L.;Achacoso, Ninah;Habel, Laurel A.
目的评估人表皮生长因子受体2（HER 2）状态的最佳方法仍存在很大争议。在报告患者HER 2结果之前，美国临床肿瘤学会（ASCO）/美国病理学家学会（CAP）指南要求实验室证明与另一个批准的实验室或方法学的一致性≥ 95%。在这里，我们比较中心实验室HER 2评估荧光原位杂交（FISH）和定量逆转录酶聚合酶链反应（RT-PCR）使用DX型在淋巴结阴性，化疗未治疗的患者从一个大型凯泽Permanente病例对照study.Patients和方法乳腺癌标本凯泽基因组健康研究进行了检查。由PhenoPath Laboratories进行HER 2扩增和17型多体性的中心FISH评估（比值> 2.2、1.8至2.2和< 1.8分别定义为HER 2阳性、HER 2可疑和HER 2阴性）。使用Genomic Health的Oncotype DX通过RT-PCR进行HER 2表达（标准化表达单位>= 11.5、10.7至< 11.5和< 10.7分别定义HER 2阳性、HER 2可疑和HER 2阴性）。结果中心FISH和中心RT-PCR检测的HER 2符合率为97%（95%CI，96%~ 99%）。RT-PCR和FISH检测分别有12%（67/568例患者）和11%（60/568例患者）的患者为HER 2阳性。与HER 2阴性患者相比，HER 2阳性患者死于乳腺癌的几率增加。12.5%的患者和33%的FISH阳性患者中证实了17号多体性。20例FISH阳性的17号染色体多体性患者中有19例同时为RT-PCR HER 2阳性。虽然没有统计学显著差异，HER 2阳性/多体性17患者往往有最差的预后，其次是HER 2阳性/eusomic，HER 2阴性/多体性17，和HER 2阴性/eusomic patients.Conclusion中心FISH和定量RT-PCR之间有高度的一致性，使用Oncotype DX的HER 2状态，和测定需要在曲妥珠单抗治疗的人群中进行额外的研究。
Purpose The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate >= 95% concordance to another approved laboratory or methodology. Here, we compare central laboratory HER2 assessed by fluorescence in situ hybridization (FISH) and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using Oncotype DX in lymph nodenegative, chemotherapy-untreated patients from a large Kaiser Permanente case-control study.Patients and Methods Breast cancer specimens from the Kaiser-Genomic Health study were examined. Central FISH assessment of HER2 amplification and polysomy 17 was conducted by PhenoPath Laboratories (ratios > 2.2, 1.8 to 2.2, and < 1.8 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). HER2 expression by RT-PCR was conducted using Oncotype DX by Genomic Health (normalized expression units >= 11.5, 10.7 to < 11.5, and < 10.7 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). Concordance analyses followed ASCO/CAP guidelines.Results HER2 concordance by central FISH and central RT-PCR was 97% (95% CI, 96% to 99%). Twelve percent (67 of 568 patients) and 11% (60 of 568 patients) of patients were HER2 positive by RT-PCR and FISH, respectively. HER2-positive patients had increased odds of dying from breast cancer compared with HER2-negative patients. Polysomy 17 was demonstrated in 12.5% of all patients and 33% of FISH-positive patients. Nineteen of 20 FISH-positive patients with polysomy 17 were also RT-PCR HER2 positive. Although not statistically significantly different, HER2positive/polysomy 17 patients tended to have the worst prognosis, followed by HER2-positive/eusomic, HER2-negative/polysomy 17, and HER2-negative/eusomic patients.Conclusion There is a high degree of concordance between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status, and the assay warrants additional study in a trastuzumab-treated population.