Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, INSERM UMR89, IFR137, Marseille, France.
Int J Cancer. 2012 Jan 1;130(1):96-104. doi: 10.1002/ijc.25979.
Medullary breast cancer (MBC) is a basal-like breast carcinoma (BLBC) with a favourable outcome, whereas nonmedullary BLBC has a poor prognosis. Tumour infiltrating lymphocytes (TILs) are present in both MBC and BLBC. We hypothesized that the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) could modulate the TILs effects among these tumours and explain their different outcomes. The amount of TILs and IDO expression were analysed using immunohistochemistry (IHC) in 155 BC cases including MBC (n = 17), atypical MBC (n = 13) and non-MBC (n = 125). Messenger RNA expression of the INDO gene, which encodes IDO, was measured in 262 cases from our institution. INDO mRNA expression and histoclinical data of 1,487 BC cases were collected from public databases. IDO immunostaining was present in both neoplastic and stromal cells in 100% of MBC and was associated with histological medullary features among non-MBC cases. There was a significant correlation between IDO positivity and TIL amounts. In our series including mostly grade-3 BC, IDO immunostaining was the most significant marker (p = 0.02) associated with better survival in multivariate analysis. Among our 262 analysed BC cases, INDO mRNA showed significant overexpression in BLBC as compared to luminal A tumours, and in MBC as compared to basal-like non-MBC. In the pooled series of 1,749 BC cases, INDO mRNA was overexpressed in BLBC and was the most significant predictor of better survival in this subtype using multivariate analysis (p = 0.0024). In conclusion, high IDO expression is associated with morphological medullary features and has an independent favourable prognostic value in BLBC.
髓样乳腺癌(MBC)是一种基底样乳腺癌(BLBC),预后良好,而非髓样 BLBC 则预后较差。肿瘤浸润淋巴细胞(TILs)存在于 MBC 和 BLBC 中。我们假设,免疫抑制酶吲哚胺 2,3-双加氧酶(IDO)可以调节这些肿瘤中的 TILs 效应,并解释它们不同的结果。我们使用免疫组织化学(IHC)分析了 155 例 BC 病例(包括 MBC[ n = 17]、非典型 MBC[ n = 13]和非 MBC[ n = 125])中 TILs 和 IDO 表达的量。我们还从我们机构的 262 例病例中测量了编码 IDO 的 INDO 基因的信使 RNA 表达。我们从公共数据库中收集了 1,487 例 BC 病例的 INDO 免疫染色和组织临床数据。在 100%的 MBC 中,IDO 免疫染色存在于肿瘤和基质细胞中,并且与非 MBC 病例的组织学髓样特征相关。IDO 阳性与 TIL 数量之间存在显著相关性。在我们的系列研究中,包括大多数 3 级 BC,IDO 免疫染色是最显著的标志物(p = 0.02),在多变量分析中与更好的生存相关。在我们分析的 262 例 BC 病例中,与 luminal A 肿瘤相比,BLBC 中 INDO mRNA 表达显著上调,与基底样非 MBC 相比,MBC 中 INDO mRNA 表达也显著上调。在 1,749 例 BC 病例的汇总系列中,BLBC 中 INDO mRNA 表达上调,在多变量分析中是该亚型更好生存的最显著预测因子(p = 0.0024)。总之,高 IDO 表达与形态学髓样特征相关,在 BLBC 中具有独立的有利预后价值。