Department of Pathology, Institut Curie, PSL Research University, Paris, France.
INSERM U934, Institut Curie, PSL Research University, Paris, France; Department of Translational Research, Institut Curie, PSL Research University, Paris, France.
Am J Pathol. 2018 Oct;188(10):2378-2391. doi: 10.1016/j.ajpath.2018.06.021. Epub 2018 Aug 1.
Medullary breast carcinoma (MBC) is a rare subtype of triple-negative breast cancer with specific genomic features within the spectrum of basal-like carcinoma (BLC). In this study of 19 MBCs and 36 non-MBC BLCs, we refined the transcriptomic and genomic knowledge about this entity. Unsupervised and supervised analysis of transcriptomic profiles confirmed that MBC clearly differs from non-MBC BLC, with 92 genes overexpressed and 154 genes underexpressed in MBC compared with non-MBC BLC. Immunity-related pathways are the most differentially represented pathways in MBC compared with non-MBC BLC. The proapoptotic gene BCLG (official name BCL2L14) is by far the most intensely overexpressed gene in MBC. A quantitative RT-PCR validation study conducted in 526 breast tumors corresponding to all molecular subtypes documented the specificity of BCLG overexpression in MBC, which was confirmed at the protein level by immunohistochemistry. We also found that most MBCs belong to the immunomodulatory triple-negative breast cancer subtype. Using pan-genomic analysis, it was found that MBC harbors more losses of heterozygosity than non-MBC BLC. These observations corroborate the notion that MBC remains a distinct entity that could benefit from specific treatment strategies (such as deescalation or targeted therapy) adapted to this rare tumor type.
乳腺髓样癌（MBC）是一种罕见的三阴性乳腺癌亚型，具有基底样癌（BLC）范围内的特定基因组特征。在这项对 19 例 MBC 和 36 例非 MBC BLC 的研究中，我们深化了对该实体的转录组和基因组知识。对转录组谱的无监督和有监督分析证实，MBC 与非 MBC BLC 明显不同，与非 MBC BLC 相比，MBC 中 92 个基因过表达，154 个基因低表达。与非 MBC BLC 相比，免疫相关途径是 MBC 中差异最显著的途径。促凋亡基因 BCLG（官方名称 BCL2L14）是迄今为止在 MBC 中表达最强烈的基因。在对所有分子亚型的 526 例乳腺肿瘤进行的定量 RT-PCR 验证研究中，记录了 BCLG 在 MBC 中的特异性过表达，免疫组织化学证实了这一点。我们还发现，大多数 MBC 属于免疫调节性三阴性乳腺癌亚型。通过全基因组分析发现，MBC 比非 MBC BLC 具有更多的杂合性丢失。这些观察结果证实了 MBC 仍然是一种独特的实体，可能受益于针对这种罕见肿瘤类型的特定治疗策略（如降级或靶向治疗）。
