免疫组织化学染色在乳腺癌分子分型中的应用

doi:10.3877/cma.j.issn.1674-0807.2018.01.002

基因表达谱研究将浸润性乳腺癌划分为5个内源性亚型：luminal A型、luminal B型、正常乳腺样型、HER-2过表达型和基底细胞样型。各亚型的发病率、预后和治疗反应性各不相同。免疫组织化学染色可以替代基因表达谱将乳腺癌划分为luminal型、HER-2亚型和三阴性亚型，最常使用的标志物是ER、PR和HER-2。通过Ki67、CK5和表皮生长因子受体(EGFR)可以区分luminal A型和luminal B型乳腺癌及区分基底细胞样型乳腺癌和不能分类的三阴性乳腺癌。近期研究使用如雄激素受体、p53等标志物可以对乳腺癌进行分子亚型分层。尽管基于免疫组织化学染色的分子分型具有临床意义，其分型结果也类似于基因表达谱确定的乳腺癌分子分型，但该类分型也存在较大的局限性：(1)缺乏各亚型名称的标准化；(2)缺乏各亚型定义的统一标准；(3)缺乏各免疫标志物统一的阳性界值。通过对相关英文文献的评读，笔者提出了一组简单、易行的基于免疫组织化学染色的乳腺癌分子分型，包括ER阳性乳腺癌、HER-2阳性乳腺癌和三阴性乳腺癌及其亚型。

关键词: 乳腺肿瘤, 分子分型, 免疫组织化学

Five intrinsic subtypes of invasive breast cancers have been identified by gene expression profiling: luminal A, luminal B, normal breast-like, HER-2-overexpressing and basal-like subtypes. The different subtypes present the different incidence, prognosis and response to therapy. Immunohistochemical staining has been used as the surrogates for gene expression profiling to divide breast cancer into luminal, HER-2 and triple-negative subtypes. ER, PR and HER-2 are the most commonly used immunohistochemical markers. Ki67, CK5 and epidermal growth factor receptor (EGFR) are useful in distinguishing luminal A from luminal B subtype and distinguishing basal-like subtype from unclassified triple-negative breast cancer. More recently, biomarkers such as androgen receptor (AR) and p53 have been shown to further stratify these molecular subtypes. Although immunohistochemistry-based molecular classification has displayed clinical significance similar to gene expression profiling-defined molecular classification, it has the following limitations: a lack of standardization in nomenclature, a lack of standardized definitions for different subtypes and no standardized cutoff value for each biomarker. With reviewing recent English language literature, a panel of immunohistochemistry-based molecular subtypes is proposed, including ER positive breast cancer, HER-2 positive breast cancer, triple-negative breast cancer and their subgroups.

Key words: Breast neoplasms, Molecular typing, Immunohistochemistry

表1 基于免疫组织化学染色的乳腺癌分子分型

免疫标志物	luminalA型	luminalB型	luminalHER-2型	HER-2富集型	BLBC	TNBC
ER	＋	＋	＋	－	－	－
PR	≥20%	<20%	＋/－	－	－	－
Ki67	<14%	≥14%	/	/	/	/
HER-2	－	－	＋	＋	－	－
CK5	/	/	/	/	＋	－
EGFR	/	/	/	/	＋	－

表1 基于免疫组织化学染色的乳腺癌分子分型

免疫标志物	luminalA型	luminalB型	luminalHER-2型	HER-2富集型	BLBC	TNBC
ER	＋	＋	＋	－	－	－
PR	≥20%	<20%	＋/－	－	－	－
Ki67	<14%	≥14%	/	/	/	/
HER-2	－	－	＋	＋	－	－
CK5	/	/	/	/	＋	－
EGFR	/	/	/	/	＋	－

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Immunohistochemical staining for molecular classification of breast cancer

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