Layfield Lester J, Schmidt Robert L
Department of Pathology, University of Utah, USA.
Appl Immunohistochem Mol Morphol. 2012 Dec;20(6):543-9. doi: 10.1097/PAI.0b013e31824d04e8.
College of American Pathologists published guidelines for the assessment of HER2/neu genetic heterogeneity. When 20 cells are counted for evaluation of HER2/neu amplification, a single 3:1 HER2/CEP17 ratio cell characterizes the sample as heterogneous. Heterogeneity for HER2/neu amplification may indicate biologically important characteristics including likelihood of amplification in metastases. We performed fluorescence in situ hybridization on 1546 cases. For each case, 20 cells of invasive carcinoma were analyzed for HER2/CEP17 ratio. Cases were assessed as nonamplified (ratio<1.8), borderline amplified (1.8 ≤ ratio ≤ 2.2), or amplified (ratio>2.20). Heterogeneity was present when the percentage of cell with ratios >2.20 was ≥5% but <50%. Individual cells were typed by probe ratios and distribution of cell types determined. The distribution of HER2/CEP17 ratio was determined with the number of 3:1 HER2/CEP17 cells plotted against the number of amplified cells. 3:1 HER2/CEP17 ratio cells occur with low frequency (2.2%) but are the determining factor for heterogeneity in 46% of heterogenous cases. Thirty-five percent of heterogenous cases were due to a single 3:1 cell. Single 3:1 cells are a poor predictor for additional amplified cells. Inclusion of cells with a 3:1 HER2/CEP17 ratio in the definition of heterogeneity may be too broad as these cells are the determining factor in approximately one third of diagnoses of heterogeneity but are not strongly associated with other measures of amplification. Moreover, 3:1 HER2/CEP17 ratio cells are a poor predictor for the presence of additional amplified cells in a sample.
美国病理学家学会发布了评估HER2/neu基因异质性的指南。当计数20个细胞以评估HER2/neu扩增时，单个HER2/CEP17比例为3:1的细胞可将样本判定为异质性。HER2/neu扩增的异质性可能表明具有生物学重要特征，包括转移灶中扩增的可能性。我们对1546例病例进行了荧光原位杂交。对于每例病例，分析20个浸润性癌细胞的HER2/CEP17比例。病例被评估为非扩增（比例<1.8）、临界扩增（1.8≤比例≤2.2）或扩增（比例>2.20）。当比例>2.20的细胞百分比≥5%但<50%时，存在异质性。通过探针比例对单个细胞进行分型，并确定细胞类型的分布。HER2/CEP17比例的分布通过将3:1的HER2/CEP17细胞数量与扩增细胞数量进行绘制来确定。3:1的HER2/CEP17比例细胞出现频率较低（2.2%），但在46%的异质性病例中是异质性的决定因素。35%的异质性病例是由于单个3:1细胞。单个3:1细胞对额外扩增细胞的预测能力较差。在异质性定义中纳入HER2/CEP17比例为3:1的细胞可能过于宽泛，因为这些细胞在大约三分之一的异质性诊断中是决定因素，但与其他扩增指标的相关性不强。此外，3:1的HER2/CEP17比例细胞对样本中额外扩增细胞的存在预测能力较差。
