Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Department of pathology, Leiden University Medical Center, Leiden, The Netherlands.
Br J Cancer. 2014 Jul 29;111(3):532-8. doi: 10.1038/bjc.2014.338. Epub 2014 Jun 17.
Classical patient and tumour characteristics are the benchmark of personalised breast cancer (BC) management. Recent evidence has demonstrated that immune and molecular profiling of BC may also play an important role. Despite evidence of differences between invasive ductal (IDC) and lobular (ILC) BC, they are infrequently accounted for when making treatment decisions for individual patients. The purpose of this study was to investigate the relevance of the tumour immune response in the major histological subtypes of BC. We also assessed the relationship between immune responses and molecular subtypes and their prognostic potential.
Immunostains were done for HLA-I, HLA-E, HLA-G, Tregs, NK cells and CTLs for the composition of the immune profiles and Ki67, EGFR, CK5/6, ER, PR and HER2 for molecular profiles in 714 breast cancer patients who underwent primary surgery.
No significant association was found between IDC (90.6%) and ILC (9.4%) and tumour immune subtypes (P=0.4) and molecular subtypes (P=0.4). However, for the relapse-free period (RFP) tumour immune subtyping was prognostic (P=0.002) in IDC, but not ILC. Contrary to ILC, IDC patients frequently expressed higher cleaved caspase-3 and Ki67, which was prognostic. Intermediate immune-susceptible IDC expressing high cleaved caspase-3 or Ki67 showed worse RFP than those with low expression (caspase-3: P=0.004; Ki67: P=0.002); this was not seen for ILC or in high or low immune-susceptible tumour types for either IDC or ILC.
Tumour immune characteristics and host immune responses are prognostic in IDC, but not ILC. In addition, tumour immune profiles are only prognostic in Luminal A tumours.
经典的患者和肿瘤特征是个性化乳腺癌(BC)管理的基准。最近的证据表明,BC 的免疫和分子分析也可能发挥重要作用。尽管浸润性导管(IDC)和小叶(ILC)BC 之间存在差异的证据,但在为个别患者做出治疗决策时,这些差异通常并未得到考虑。本研究旨在探讨肿瘤免疫反应在 BC 主要组织学亚型中的相关性。我们还评估了免疫反应与分子亚型之间的关系及其预后潜力。
对 714 名接受原发性手术的乳腺癌患者的肿瘤免疫谱进行 HLA-I、HLA-E、HLA-G、Tregs、NK 细胞和 CTL 的免疫染色,以及 Ki67、EGFR、CK5/6、ER、PR 和 HER2 的分子谱。
IDC(90.6%)和 ILC(9.4%)与肿瘤免疫亚型(P=0.4)和分子亚型(P=0.4)之间没有显著关联。然而,对于无复发生存期(RFP),肿瘤免疫亚分型在 IDC 中具有预后意义(P=0.002),但在 ILC 中没有。与 ILC 相反,ID C 患者经常表达更高的裂解 caspase-3 和 Ki67,这具有预后意义。表达高裂解 caspase-3 或 Ki67 的中间免疫敏感 IDC 患者的 RFP 比低表达的患者差(caspase-3:P=0.004;Ki67:P=0.002);对于 ILC 或 IDC 或 ILC 的高或低免疫敏感肿瘤类型,均未观察到这种情况。
肿瘤免疫特征和宿主免疫反应在 IDC 中具有预后意义,但在 ILC 中没有。此外,肿瘤免疫谱仅在 Luminal A 肿瘤中具有预后意义。