Genentech, South San Francisco, CA.
Ventana Medical Systems, Tucson, AZ.
Appl Immunohistochem Mol Morphol. 2021 Apr 1;29(4):258-264. doi: 10.1097/PAI.0000000000000857.
Metastatic triple-negative breast cancer (mTNBC) is the most aggressive breast cancer subtype. Programmed death ligand 1 (PD-L1) on immune cells (IC) using the VENTANA SP142 assay is linked to improved clinical outcome in atezolizumab plus nab-paclitaxel-treated patients with mTNBC in the IMpassion130 study. The goal of the current study was to evaluate prevalence of VENTANA SP142 PD-L1 assay by anatomic location in 670 histologically confirmed TNBC cases from subjects with metastatic disease screened for the phase 1 study PCD4989g (NCT01375842). PD-L1 immunohistochemistry was centrally tested on tumor cells (TC) and on tumor infiltrating IC, following manufacturer's instructions. At a 1% cutoff, tumor PD-L1 was more prevalent in IC than TC: 46% were PD-L1 IC+/TC-, 3% were PD-L1 IC-/TC+, and 10% were PD-L1 IC+/TC+. PD-L1 IC and TC immunostaining correlated with CD274 RNA expression, as assessed by fluidigm. Analyses of anatomic locations suggest that prevalence of PD-L1 IC+ was highest in lymph nodes (65.0%), lowest in liver metastases (26.9%), while breast tissue was intermediate (57.1%). Matched paired samples from the same subject collected synchronously or asynchronously showed a PD-L1 IC status agreement of 80% (8/10) and 75% (15/20), respectively. Our results suggest that the anatomic location of metastases and time of collection may influence the detection of PD-L1.
转移性三阴性乳腺癌（mTNBC）是最具侵袭性的乳腺癌亚型。在 IMpassion130 研究中，使用 VENTANA SP142 检测免疫细胞（IC）上的程序性死亡配体 1（PD-L1）与阿特珠单抗联合 nab-紫杉醇治疗 mTNBC 患者的临床获益相关。本研究的目的是评估在转移性疾病筛选的 I 期研究 PCD4989g（NCT01375842）中，670 例组织学证实的 TNBC 病例中，根据解剖部位评估 VENTANA SP142 PD-L1 检测的阳性率。根据制造商的说明，对肿瘤细胞（TC）和肿瘤浸润性 IC 进行 PD-L1 免疫组化检测。在 1%的截定点上，IC 中的肿瘤 PD-L1 比 TC 更为常见：46%为 PD-L1 IC+/TC-，3%为 PD-L1 IC-/TC+，10%为 PD-L1 IC+/TC+。PD-L1 IC 和 TC 免疫染色与 Fluidigm 评估的 CD274 RNA 表达相关。解剖部位分析表明，PD-L1 IC+的阳性率在淋巴结中最高（65.0%），在肝转移中最低（26.9%），而在乳腺组织中处于中间水平（57.1%）。从同一患者同步或异步收集的配对样本显示，PD-L1 IC 状态的一致性分别为 80%（8/10）和 75%（15/20）。我们的结果表明，转移部位的解剖位置和采集时间可能会影响 PD-L1 的检测。
