From the Division of Molecular Pathology (Drs Pai, Shetty, Singh, and Desai) and the Department of Pathology (Drs Pai, Shet, Patil, Shetty, Singh, and Desai), Tata Memorial Centre, Mumbai, India.
Arch Pathol Lab Med. 2018 May;142(5):626-633. doi: 10.5858/arpa.2017-0252-OA. Epub 2018 Jan 31.
Context PathVysion-a US Food and Drug Administration-approved dual-probe human epidermal growth factor receptor ( HER2) fluorescence in situ hybridization (FISH) assay-provides the HER2: CEP17 ratio, a centromeric enumeration probe ratio for determining HER2 status in breast cancers. However, pericentromeric amplifications might then skew the HER2: CEP17 ratio, underestimating the HER2 status, which calls into question the use of CEP17 as the reference probe. Objective To analyze the utility of a noncentromeric chromosome 17 reference locus ( D17S122) to assess HER2 gene status in cases showing "nonclassical" FISH patterns with the CEP17 probe. Design The HER2 status of breast cancers accessioned in the years 2015-2017, displaying "nonclassical" or "equivocal" results by the PathVysion (Abbott Molecular Inc, Des Plaines, Illinois) HER2 DNA Probe Kit were reflex tested using an alternate FISH probe (ZytoLight SPEC/D17S122, ZytoVision, Bremerhaven, Germany) and interpreted with American Society of Clinical Oncology/College of American Pathologists 2013 guidelines. Results Of 37 cases, 17 were FISH equivocal. With the alternate D17S122 probe, 13 (76.4%) were reclassified as amplified, 3 (17.6%) as nonamplified, and a single case retained an equivocal result. Of the 17 cases with a chromosome 17 polysomy pattern, disomy, polysomy, and monosomy patterns were seen with 14 cases, 2 cases, and 1 case, respectively. Within the 17 cases with polysomy pattern, 3 (17.6%) demonstrated an unusual colocalization pattern of HER2 and CEP17, which was not observed with the alternate probe. Conclusions The denominator-stable alternate probe is a useful adjunct in the diagnostic armamentarium to analyze HER2 status in cases with FISH equivocal and complex patterns.
PathVysion——一种获得美国食品和药物管理局批准的双探针人表皮生长因子受体（HER2）荧光原位杂交（FISH）检测方法——提供了 HER2：CEP17 比值，这是一种用于确定乳腺癌中 HER2 状态的着丝粒计数探针比值。然而，着丝粒周围的扩增可能会扭曲 HER2：CEP17 比值，从而低估 HER2 状态，这使得 CEP17 作为参考探针的使用受到质疑。目的 分析非着丝粒染色体 17 参考位点（D17S122）在使用 CEP17 探针显示“非典型”FISH 模式的情况下评估 HER2 基因状态的实用性。设计 对 2015 年至 2017 年入组的乳腺癌病例进行 HER2 状态分析，这些病例的 PathVysion（雅培分子公司，伊利诺伊州德斯普兰斯）HER2 DNA 探针试剂盒显示“非典型”或“不确定”结果，采用替代 FISH 探针（ZytoLight SPEC/D17S122，ZytoVision，不来梅港，德国）进行反射性检测，并按照美国临床肿瘤学会/美国病理学家学院 2013 年指南进行解读。结果 37 例病例中，17 例 FISH 结果不确定。使用替代的 D17S122 探针，13 例（76.4%）被重新分类为扩增，3 例（17.6%）为非扩增，1 例保持不确定结果。在 17 例染色体 17 三体模式的病例中，分别有 14 例、2 例和 1 例出现单体、三体和单体模式。在 17 例存在三体模式的病例中，有 3 例（17.6%）显示出 HER2 和 CEP17 的异常共定位模式，而这种模式在替代探针中没有观察到。结论 对于 FISH 不确定和复杂模式的病例，稳定的替代探针是分析 HER2 状态的有用辅助手段。
