Division of Clinical Pathology, Hôpitaux Universitaire de Genève, Genève, Switzerland.
Pathology-Genetics-Immunology Department, Institut Curie, PSL Research University, Paris, France.
Mod Pathol. 2020 Nov;33(11):2198-2207. doi: 10.1038/s41379-020-0561-9. Epub 2020 May 13.
The prognostic impact of tumor-infiltrating lymphocytes (TILs) within invasive lobular carcinoma (ILC) remains to be better characterized. In estrogen receptor (ER)-negative invasive ductal carcinomas of no special type (IDC-NST), TILs are associated with good prognosis. The aim of this study was to examine TILs in ILC, with particular focus on prognostic and clinicopathologic features. A cohort comprising 459 consecutive ILCs diagnosed in a single institution from 2005 to 2008 met the eligibility criteria for this study. The percentage of tumor area occupied by TILs was quantified by two breast pathologists and categorized into three groups: no TILs, ≤5%, >5%. Clinicopathologic features were tested by Fisher's exact tests or Chi tests. Overall survival (OS) and invasive disease-free survival (iDFS) were estimated by Kaplan-Meier and Cox proportional hazard statistics. There were 239 TIL-negative cases, 185 cases with ≤5% TILs, and 35 cases with >5% TILs. TILs were associated with younger age, larger tumors, lymph node involvement, poor Nottingham prognostic index, HER2 amplification, multinucleation, and prominent nucleoli (p < 0.05). Poor OS was significantly associated with increasing TILs in the univariate Cox proportional hazards model (p < 0.001) and Kaplan-Meier estimator (p < 0.05, log-rank test). Similar results were observed for iDFS (p = 0.004 for Cox univariate and p = 0.005 for log-rank test). Notably, TILs can identify a subset of ILC patients with poor OS independently of molecular subtype and lymph node metastases (multivariate Cox, p < 0.001, OS hazard ratio (HR) = 4.38 and HR = 6.15, for ≤5% and >5% TILs, respectively, vs. absence of TILs). Prominent nucleoli was the only nuclear feature associated with poor OS (p = 0.05) and iDFS (p = 0.05) in univariate Cox survival analysis. TILs represent a promising new morphologic biomarker associated with poor outcome of ILC, in contrast with that observed in ER-negative IDC-NST.
肿瘤浸润淋巴细胞（TILs）在浸润性小叶癌（ILC）中的预后影响仍有待更好地描述。在雌激素受体（ER）阴性的非特殊型浸润性导管癌（IDC-NST）中，TILs 与良好的预后相关。本研究旨在研究 ILC 中的 TILs，特别关注其预后和临床病理特征。一个由 2005 年至 2008 年在一家机构诊断的 459 例连续 ILC 组成的队列符合本研究的入选标准。两名乳腺病理学家通过定量评估肿瘤区域内 TILs 的百分比，并将其分为三组：无 TILs、≤5%、>5%。通过 Fisher 确切检验或 Chi 检验测试临床病理特征。通过 Kaplan-Meier 和 Cox 比例风险统计评估总生存期（OS）和浸润性疾病无复发生存期（iDFS）。有 239 例 TIL 阴性病例、185 例 TILs≤5%和 35 例 TILs>5%。TILs 与年龄较小、肿瘤较大、淋巴结受累、不良的诺丁汉预后指数、HER2 扩增、多核和明显核仁（p<0.05）相关。在单因素 Cox 比例风险模型（p<0.001）和 Kaplan-Meier 估计器（p<0.05，对数秩检验）中，TILs 与较差的 OS 显著相关。对于 iDFS 也观察到相似的结果（Cox 单因素 p=0.004，对数秩检验 p=0.005）。值得注意的是，TILs 可以独立于分子亚型和淋巴结转移，识别出一组 OS 较差的 ILC 患者（多因素 Cox，p<0.001，OS 风险比（HR）分别为 4.38 和 6.15，TILs≤5%和>5%，与无 TILs 相比）。显著核仁是唯一与 OS（p=0.05）和 iDFS（p=0.05）相关的核特征在单因素 Cox 生存分析中。TILs 是一种有前途的新形态标志物，与 ER 阴性 IDC-NST 中观察到的结果相反，与 ILC 的不良预后相关。
