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Abstract：
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.
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.
摘要：
背景：用于乳腺癌中人类表皮生长因子受体2（HER2）基因扩增的双探针荧光原位杂交（FISH）测定法提供了HER2：CEP17（染色体17的着丝粒计数探针）比率。CEP17中的拷贝数改变(CNA)可能会扭曲该比率。作者分析了2013年美国肿瘤学会/美国病理学家学院（ASCO/CAP）指南和另一种17号染色体探针对CEP17CNA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个肿瘤样品中选择具有CEP17CNA(n=310)的样本,用于使用替代染色体17探针D17S122进行测试。使用2007年和2013年ASCO/CAP指南评估HER2状态的重新分类。
结果：使用2007年和2013年指南，替代染色体17探针对310个肿瘤中的82个（26.5％）和310个肿瘤中的87个（28.1％）进行了重新分类，分别。在根据2007年指南从非扩增到扩增的310个肿瘤中的41个（13.2%），41个中的28个(68.3%)具有平均HER2拷贝数≥4.0和<6.0。根据2013年指南，从模棱两可重新分类到扩增的310个肿瘤中有39个（12.6%）的平均HER2拷贝数在≥4.0和<6.0之间。这些病人大部分都是I期,激素受体阳性,淋巴结阴性肿瘤,这是HER2扩增肿瘤的不寻常的临床病理特征，除内分泌治疗外,大多数患者还接受了HER2靶向治疗.
结论：使用2013年ASCO/CAP指南使用替代的17号染色体探针进行的反射测试对28.1%的CEP17CNA肿瘤样本进行了重新分类，将近一半从模棱两可转变为放大。HER2靶向治疗在该患者人群中的益处需要进一步研究。癌症2017；123：2230-2239。©2017美国癌症协会。
方法:从2013年1月至2015年6月接收的3048个肿瘤样品中选择具有CEP17CNA(n=310)的样本,用于使用替代染色体17探针D17S122进行测试。使用2007年和2013年ASCO/CAP指南评估HER2状态的重新分类。
结果：使用2007年和2013年指南，替代染色体17探针对310个肿瘤中的82个（26.5％）和310个肿瘤中的87个（28.1％）进行了重新分类，分别。在根据2007年指南从非扩增到扩增的310个肿瘤中的41个（13.2%），41个中的28个(68.3%)具有平均HER2拷贝数≥4.0和<6.0。根据2013年指南，从模棱两可重新分类到扩增的310个肿瘤中有39个（12.6%）的平均HER2拷贝数在≥4.0和<6.0之间。这些病人大部分都是I期,激素受体阳性,淋巴结阴性肿瘤,这是HER2扩增肿瘤的不寻常的临床病理特征，除内分泌治疗外,大多数患者还接受了HER2靶向治疗.
结论：使用2013年ASCO/CAP指南使用替代的17号染色体探针进行的反射测试对28.1%的CEP17CNA肿瘤样本进行了重新分类，将近一半从模棱两可转变为放大。HER2靶向治疗在该患者人群中的益处需要进一步研究。癌症2017；123：2230-2239。©2017美国癌症协会。
