Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi Province, People's Republic of China.
Institute of Forensic Medicine, Shanxi Medical University, Taiyuan, Shanxi Province, People's Republic of China.
Virchows Arch. 2022 Jul;481(1):13-21. doi: 10.1007/s00428-022-03329-0. Epub 2022 Apr 26.
The molecular subtyping of triple-negative breast cancer (TNBC) is critical to guiding individualized patient treatment. In this study, we sought to characterize the clinicopathologic features of TNBC subtypes and to identify correlates of patient survival in an effort to provide a robust foundation for treatment planning. We additionally assessed PD-L1 expression in Chinese TNBC patients and evaluated the relationship between such expression and immunotherapeutic treatment outcomes. Based on analyses of histologic characteristics including apocrine differentiation, tumor-infiltrating lymphocytes, and metaplastic features, we selected immunohistochemical (IHC) markers including CD8, FOXC1, and AR for use in classifying TNBC cases. Associations between these subtypes and a range of clinicopathologic characteristics were evaluated. We classified a cohort of 93 TNBC patients into individuals with luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immune-suppressed (BLIS), and mesenchymal (MES) tumor subtypes (23, 24, 39, and 7 cases, respectively). PD-L1 positivity was observed in 49.6% of cases and was more common in individuals with IM subtype disease. Mismatch repair deficiency (dMMR) was observed in just one patient. Significant differences in histologic grade, pT stage, lymphocyte distribution patterns, large scarring areas without cells in tumor of central (central scar), and PD-L1, P53, and Rb status were observed among these TNBC subtypes, whereas no such differences were observed with respect to age, invasion pattern, or pN stage. Rates of disease progression were higher at the 40-50 month follow-up time point, but there were no significant differences in recurrence-free survival or breast cancer-specific survival among these subtypes. IHC markers associated with clinicopathologic characteristics represent a powerful approach to TNBC molecular typing, providing a foundation for precision patient treatment. PD-L1 expression may represent a relevant factor in TNBC patient immunotherapeutic treatment planning, whereas dMMR is not likely to be of substantial value when evaluating immunotherapeutic efficacy in these patients.
三阴性乳腺癌（TNBC）的分子亚型对于指导个体化患者治疗至关重要。在这项研究中，我们旨在描述 TNBC 亚型的临床病理特征，并确定与患者生存相关的因素，以期为治疗计划提供坚实的基础。我们还评估了中国 TNBC 患者的 PD-L1 表达，并评估了这种表达与免疫治疗治疗结果之间的关系。基于包括大汗腺分化、肿瘤浸润淋巴细胞和化生特征在内的组织学特征分析，我们选择了包括 CD8、FOXC1 和 AR 在内的免疫组化（IHC）标志物用于分类 TNBC 病例。评估了这些亚型与一系列临床病理特征之间的关联。我们将 93 例 TNBC 患者分为 luminal androgen receptor (LAR)、免疫调节 (IM)、基底样免疫抑制 (BLIS) 和间充质 (MES) 肿瘤亚型的个体（分别为 23、24、39 和 7 例）。观察到 49.6%的病例存在 PD-L1 阳性，并且在具有 IM 亚型疾病的个体中更为常见。仅在一名患者中观察到错配修复缺陷 (dMMR)。在这些 TNBC 亚型中，组织学分级、pT 分期、淋巴细胞分布模式、肿瘤中央无细胞大瘢痕区（中央瘢痕）以及 PD-L1、P53 和 Rb 状态存在显著差异，而在年龄、浸润模式或 pN 分期方面则无差异。在 40-50 个月的随访时间点，疾病进展率更高，但在这些亚型中，无复发生存或乳腺癌特异性生存无显著差异。与临床病理特征相关的 IHC 标志物代表了 TNBC 分子分型的有力方法，为精确的患者治疗提供了基础。PD-L1 表达可能是 TNBC 患者免疫治疗计划的一个相关因素，而 dMMR 在评估这些患者的免疫治疗疗效时可能没有太大价值。
