van der Logt Elise M J, Kuperus Deborah A J, van Setten Jan W, van den Heuvel Marius C, Boers James E, Schuuring Ed, Kibbelaar Robby E
Department of Pathology, Pathology Friesland, Leeuwarden, The Netherlands; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Pathology, Pathology Friesland, Leeuwarden, The Netherlands.
PLoS One. 2015 Apr 6;10(4):e0123201. doi: 10.1371/journal.pone.0123201. eCollection 2015.
HER2 assessment is routinely used to select patients with invasive breast cancer that might benefit from HER2-targeted therapy. The aim of this study was to validate a fully automated in situ hybridization (ISH) procedure that combines the automated Leica HER2 fluorescent ISH system for Bond with supervised automated analysis with the Visia imaging D-Sight digital imaging platform. HER2 assessment was performed on 328 formalin-fixed/paraffin-embedded invasive breast cancer tumors on tissue microarrays (TMA) and 100 (50 selected IHC 2+ and 50 random IHC scores) full-sized slides of resections/biopsies obtained for diagnostic purposes previously. For digital analysis slides were pre-screened at 20x and 100x magnification for all fluorescent signals and supervised-automated scoring was performed on at least two pictures (in total at least 20 nuclei were counted) with the D-Sight HER2 FISH analysis module by two observers independently. Results were compared to data obtained previously with the manual Abbott FISH test. The overall agreement with Abbott FISH data among TMA samples and 50 selected IHC 2+ cases was 98.8% (κ = 0.94) and 93.8% (κ = 0.88), respectively. The results of 50 additionally tested unselected IHC cases were concordant with previously obtained IHC and/or FISH data. The combination of the Leica FISH system with the D-Sight digital imaging platform is a feasible method for HER2 assessment in routine clinical practice for patients with invasive breast cancer.
人表皮生长因子受体2（HER2）评估通常用于筛选可能从HER2靶向治疗中获益的浸润性乳腺癌患者。本研究的目的是验证一种全自动原位杂交（ISH）程序，该程序将用于邦德（Bond）的徕卡HER2荧光ISH自动系统与使用Visia成像D-Sight数字成像平台的监督自动分析相结合。对组织微阵列（TMA）上的328例福尔马林固定/石蜡包埋的浸润性乳腺癌肿瘤以及之前为诊断目的获取的100张（50例筛选出的免疫组化（IHC）2+和50例随机IHC评分）全尺寸切除/活检切片进行HER2评估。对于数字分析，将玻片在20倍和100倍放大倍数下预筛选所有荧光信号，并由两名观察者使用D-Sight HER2荧光原位杂交（FISH）分析模块对至少两张图片（总共至少计数20个细胞核）进行监督自动评分。将结果与之前使用手动雅培FISH检测获得的数据进行比较。TMA样本和50例筛选出的IHC 2+病例与雅培FISH数据的总体一致性分别为98.8%（κ=0.94）和93.8%（κ=0.88）。另外50例未经筛选的IHC病例的检测结果与之前获得的IHC和/或FISH数据一致。徕卡FISH系统与D-Sight数字成像平台相结合，是浸润性乳腺癌患者常规临床实践中进行HER2评估的一种可行方法。
