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
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