Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists
Comparison of automated silver enhanced in situ hybridisation (SISH) and fluorescence ISH (FISH) for the validation of HER2 gene status in breast carcinoma according to the guidelines of the American Society of Clinical Oncology and the College of American Pathologists
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DOI：
10.1007/s00428-007-0424-5
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发表时间：
2007-07-01
期刊：
影响因子：
3.5
通讯作者：
Kristiansen, G.
中科院分区：
文献类型：
--
作者：
Dietel, M.;Ellis, I. O.;Kristiansen, G.
HER2是乳腺癌中一种重要的肿瘤标志物。然而，关于哪种方法可靠地测量HER2状态存在争议。本研究对浸润性乳腺癌中HER2基因扩增的一致性进行了评价。原位杂交（FISH）和一种新的银增强原位杂交（SISH）技术。99例患者采用直接标记的手工FISH （PathVysion (R), Abbott/Vysis）和亮场自动SISH （INFORM (R), Ventana）进行分析。为了比较，所有标本都进行免疫组化染色（Dako-HercepTest （TM）和Ventana-PATHWAY (R) 4B5）。评估由五名病理学家按照制造商的算法和美国临床肿瘤学会/美国病理学家学会（ASCO/CAP）指南进行。计算一致性，估计k统计值。FISH与SISH的总体一致性为96.0% （kappa=0.754, 95%Cl）。差异主要见于肿瘤内HER2扩增异质性的肿瘤。综上所述，通过SISH可以可靠地确定HER2基因的拷贝状态。与FISH的96%一致性符合ASCO/CAP对扩增与非扩增病例一致性大于95%的要求。在对SISH的解释中，观察者之间的可变性很低，这表明SISH在确定HER2扩增方面与FISH同样可靠。由于SISH结合了亮场显微镜与分子分析和全自动化，它似乎特别适合外科病理的常规应用。
HER2 is an important tumour marker in breast cancer. However, there is controversy regarding which method reliably measures HER2 status. This study evaluates the concordance between HER2 gene amplification in invasive breast cancer determined by fluorescence in. situ hybridisation (FISH) and a new silver enhanced in situ hybridisation (SISH) technique. Ninety-nine cases were analysed by direct-labelled manual FISH (PathVysion (R), Abbott/Vysis) and bright field automated SISH (INFORM (R), Ventana). For comparison, all specimens were stained by immunohistochemistry (Dako-HercepTest (TM) and Ventana-PATHWAY (R) 4B5). Evaluation was performed by five pathologists following the algorithms of the manufacturers and the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. Concordance was calculated and the value of K. statistics estimated. Overall concordance between FISH and SISH was 96.0% (kappa=0.754, 95%Cl). Discrepancies were mostly seen in tumours with intra-tumoural heterogeneity of HER2 amplification. In conclusion, HER2 gene copy status can be reliably determined by SISH. The 96% concordance with FISH fulfils the ASCO/CAP requirement of greater than 95% concordance for amplified vs non-amplified cases. There was a low inter-observer variability in the interpretation of SISH, suggesting that SISH is equally reliable in determining HER2 amplification as FISH. Because SISH combines bright field microscopy with molecular analysis and full automation, it appears to be particularly suited for routine application in surgical pathology.