乳腺导管原位癌赫突过表达的意义

　　根据既往研究报告，乳腺导管原位癌的HER2阳性率高达50%，但是乳腺浸润癌的HER2阳性率较低。

　　2019年5月8日，英国癌症研究基金会、英国《自然》旗下《英国癌症杂志》在线发表英国诺丁汉大学、埃及米努夫大学和阿斯由特、澳大利亚墨尔本大学和彼得麦卡伦癌症中心的研究报告，分析了乳腺导管原位癌的HER2表达特征及其临床意义和生物学意义。

　　该单中心大样本研究对用于制备组织微阵列的868例乳腺导管原位癌（包括单纯乳腺导管原位癌、混合乳腺导管原位癌）通过免疫组化和显色原位杂交分析HER2表达水平。

　　结果发现，对于单纯乳腺导管原位癌，通过免疫组化分析，HER2蛋白过表达（+++）占9%、可疑（++）占15%，通过显色原位杂交，最终HER2蛋白阳性占20%。

　　对于混合乳腺导管原位癌，乳腺导管原位癌成分HER2基因扩增占15%，乳腺浸润癌成分HER2基因扩增占12%。

　　乳腺导管原位癌HER2阳性的显著相关因素包括：

• 肿瘤较大（P<0.0001）

• 核分级高（P<0.0001）

• 粉刺坏死（P<0.0001）

• 激素受体（P<0.0001）

• 增殖指数（P<0.0001）

• 局部复发（P=0.03）

　　根据多因素分析，HER2阳性且增殖指数（Ki67）较高是局部复发的独立预测因素（P=0.006）。

　　因此，该研究结果表明，乳腺导管原位癌与乳腺浸润癌相比，HER2阳性率相似，HER2阳性乳腺导管原位癌与预后不良特征相关，乳腺导管原位癌HER2蛋白过表达主要由HER2基因扩增造成。

Br J Cancer. 2019 May 8. [Epub ahead of print]

The clinical and biological significance of HER2 over-expression in breast ductal carcinoma in situ: a large study from a single institution.

Islam M. Miligy, Michael S. Toss, Kylie L. Gorringe, Andrew H. S. Lee, Ian O. Ellis, Andrew R. Green, Emad A. Rakha.

The University of Nottingham, Nottingham, UK; Menoufia University, Menoufia, Egypt; Assiut University, Assiut, Egypt; Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Parkville, Australia.

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.

DOI: 10.1038/s41416-019-0436-3