HER2 过表达在乳腺导管原位癌中的临床和生物学意义：来自单一机构的大型研究。
The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution.
机构信息
Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, Nottingham City Hospital, The University of Nottingham, Nottingham, UK.
Histopathology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
出版信息
Br J Cancer. 2019 May;120(11):1075-1082. doi: 10.1038/s41416-019-0436-3. Epub 2019 May 8.
BACKGROUND
Previous studies have reported up to 50% of ductal carcinoma in situ (DCIS), is HER2 positive, but the frequency of HER2-positive invasive breast cancer (IBC) is lower. The aim of this study is to characterise HER2 status in DCIS and assess its prognostic value.
METHODS
HER2 status was evaluated in a large series of DCIS (n = 868), including pure DCIS and DCIS associated with IBC, prepared as tissue microarrays (TMAs). HER2 status was assessed using immunohistochemistry (IHC) and chromogenic in situ hybridisation (CISH).
RESULTS
In pure DCIS, HER2 protein was over-expressed in 9% of DCIS (3+), whereas 15% were HER2 equivocal (2+). Using CISH, the final HER2 status was positive in 20%. In mixed DCIS, HER2 amplification of the DCIS component was detected in 15% with amplification in the invasive component of only 12%. HER2-positive DCIS was associated with features of aggressiveness (p < 0.0001) and more frequent local recurrence (p = 0.03). On multivariate analysis, combined HER2+/Ki67+ profile was an independent predictor of local recurrence (p = 0.006).
CONCLUSIONS
The frequency of HER2 positivity in DCIS is comparable to IBC- and HER2-positive DCIS is associated with features of poor prognosis. The majority of HER2 over-expression in DCIS is driven by gene amplification.
背景
先前的研究报告称，多达 50%的导管原位癌（DCIS）为 HER2 阳性，但 HER2 阳性浸润性乳腺癌（IBC）的频率较低。本研究旨在描述 DCIS 中的 HER2 状态，并评估其预后价值。
方法
使用组织微阵列（TMA）评估了大量 DCIS（n=868）中的 HER2 状态，包括纯 DCIS 和与 IBC 相关的 DCIS。使用免疫组织化学（IHC）和显色原位杂交（CISH）评估 HER2 状态。
结果
在纯 DCIS 中，9%的 DCIS（3+）HER2 蛋白过表达，而 15%的 HER2 状态不确定（2+）。使用 CISH，最终 HER2 状态阳性率为 20%。在混合 DCIS 中，仅检测到 DCIS 成分的 HER2 扩增，其阳性率为 15%，而浸润性成分的 HER2 扩增率为 12%。HER2 阳性的 DCIS 与侵袭性特征（p<0.0001）和更高的局部复发率（p=0.03）相关。多变量分析显示，HER2+/Ki67+联合表型是局部复发的独立预测因子（p=0.006）。
结论
DCIS 中 HER2 阳性的频率与 IBC 相似，并且 HER2 阳性的 DCIS 与不良预后特征相关。DCIS 中 HER2 过表达的大多数是由基因扩增驱动的。
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