一种替代性17号染色体探针及2013年美国临床肿瘤学会和美国病理学家学会指南对荧光原位杂交检测乳腺癌HER2基因扩增的影响
Impact of an alternative chromosome 17 probe and the 2013 American Society of Clinical Oncology and College of American Pathologists guidelines on fluorescence in situ hybridization for the determination of HER2 gene amplification in breast cancer.
作者信息
Donaldson Alana R, Shetty Shashirekha, Wang Zhen, Rivera Christine L, Portier Bryce P, Budd G Thomas, Downs-Kelly Erinn, Lanigan Christopher P, Calhoun Benjamin C
机构信息
Department of Pathology, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
Department of Laboratory Medicine, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
出版信息
Cancer. 2017 Jun 15;123(12):2230-2239. doi: 10.1002/cncr.30592. Epub 2017 Feb 13.
BACKGROUND
The dual-probe fluorescence in situ hybridization (FISH) assay for human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer provides an HER2:CEP17 (centromere enumeration probe for chromosome 17) ratio. Copy number alteration (CNA) in CEP17 may skew this ratio. The authors analyzed the impact of the 2013 American Society of Oncology/College of American Pathologists (ASCO/CAP) guidelines and an alternative chromosome 17 probe on HER2 status in tumor specimens with CEP17 CNA.
METHODS
Specimens with CEP17 CNA (n = 310) were selected from 3048 tumor samples that were received from January 2013 to June 2015 for testing with the alternative chromosome 17 probe D17S122. Reclassification of HER2 status was assessed using the 2007 and 2013 ASCO/CAP guidelines.
RESULTS
The alternative chromosome 17 probe reclassified 82 of 310 (26.5%) and 87 of 310 (28.1%) tumors using the 2007 and 2013 guidelines, respectively. Of the 41 of 310 tumors (13.2%) that were reclassified from nonamplified to amplified according to 2007 guidelines, 28 of 41 (68.3%) had an average HER2 copy number ≥4.0 and <6.0. The 39 of 310 tumors (12.6%) that were reclassified from equivocal to amplified according to 2013 guidelines had a mean HER2 copy number between ≥4.0 and <6.0. Most of these patients had stage I, hormone receptor-positive, lymph node-negative tumors, which is an unusual clinicopathologic profile for HER2-amplified tumors, and most received HER2-targeted therapy in addition to endocrine therapy.
CONCLUSIONS
Reflex testing with an alternative chromosome 17 probe using the 2013 ASCO/CAP guidelines reclassified 28.1% of tumor samples that had CEP17 CNA, converting nearly one-half from equivocal to amplified. The benefit of HER2-targeted therapy in this patient population requires further study. Cancer 2017;123:2230-2239. © 2017 American Cancer Society.
背景
用于检测乳腺癌中人表皮生长因子受体2（HER2）基因扩增的双探针荧光原位杂交（FISH）检测可得出HER2:CEP17（17号染色体着丝粒计数探针）比值。CEP17中的拷贝数改变（CNA）可能会使该比值出现偏差。作者分析了2013年美国临床肿瘤学会/美国病理学家协会（ASCO/CAP）指南以及另一种17号染色体探针对存在CEP17 CNA的肿瘤标本中HER2状态的影响。
方法
从2013年1月至2015年6月接收的3048份肿瘤样本中选取存在CEP17 CNA的标本（n = 310），使用另一种17号染色体探针D17S122进行检测。采用2007年和2013年ASCO/CAP指南评估HER2状态的重新分类情况。
结果
根据2007年和2013年指南，另一种17号染色体探针分别对310例肿瘤中的82例（26.5%）和87例（28.1%）进行了重新分类。在310例肿瘤中，根据2007年指南从非扩增重新分类为扩增的41例（13.2%）中，41例中的28例（68.3%）平均HER2拷贝数≥4.0且<6.0。根据2013年指南从不确定重新分类为扩增的310例肿瘤中的39例（12.6%），其平均HER2拷贝数在≥4.0至<6.0之间。这些患者大多患有I期、激素受体阳性、淋巴结阴性肿瘤，这对于HER2扩增肿瘤来说是不寻常的临床病理特征，并且大多数患者除接受内分泌治疗外还接受了HER2靶向治疗。
结论
按照2013年ASCO/CAP指南使用另一种17号染色体探针进行的回顾性检测对310例存在CEP17 CNA的肿瘤样本中的28.1%进行了重新分类，将近一半从不明确变为扩增。HER2靶向治疗在该患者群体中的益处需要进一步研究。《癌症》2017年；123:2230 - 2239。© 2017美国癌症协会。
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