Montero M Angeles, Aricak Ozan, Kis Lorand, Yoshikawa Akira, De Petris Luigi, Grundberg Oscar, Pham Hoa H N, Roden Anja C, Fukuoka Junya, Attanoos Richard, Guijarro Ricardo, Alarcón Felix, Lindström Kati, Ortiz-Villalón Cristian
Department of Histopathology, Manchester University NHS Foundation Trust, UK.
Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden.
Ann Diagn Pathol. 2021 Apr;51:151701. doi: 10.1016/j.anndiagpath.2021.151701. Epub 2021 Jan 9.
PD1/PD-L1 pathway targeting therapies are nowadays an established treatment option for patients with NSCLC. We assessed whether PD-L1 expression in NSCLC tumor cells was associated with specific clinical features or overall survival using four different clones.
A retrospective study included formalin-fixed paraffin embedded (FFPE) surgical tumors from 482 patients. PD-L1 status was assessed with immunohistochemistry in tumor cells on tissue microarrays using clones 28-8, 22C3, SP263 and SP142. Associations with OS were assessed by Kaplan-Meier and multivariate Cox's regression analysis. Patients' median age: 68 years (39-86); histology: adenocarcinoma (AdCa) 61%, squamous-cell carcinoma (SqCC) 33%, and large cell carcinoma (LCC) 6%; p-stage: IA (46%), IB (30%), IIA (10%), IIB (11,4%), IIIA (1,2%), IIIB - IV (0,4%). PD-L1 positivity (≥1%) in NSCLC for clones 28-8, 22C3, SP263, SP142 was 41.5%, 34.2%, 42.7%, 10.4%, respectively (Pearson Chi-square p < 0.0001). PD-L1 expression was correlated with histology, tumor size and grading. Statistically significant association between PD-L1 expression and OS in NSCLC and Non-AdCa was observed with clone SP142 (log-rank p = 0.045 and p = 0.05, respectively). Statistically significant association between PD-L1 expression and OS in LCC was observed with clones 22C3 (log-rank p = 0.009) and SP263 (log-rank p = 0.050).
Overexpression of the PD-L1 clone SP142 was associated with poor overall survival in NSCLC and Non-AdCa. Clones 22C3 and SP263 were associated with poor prognosis in LCC. PD-L1 status might serve as a prognostic marker in NSCLC.
如今，PD1/PD-L1通路靶向疗法是NSCLC患者既定的治疗选择。我们使用四种不同克隆评估了NSCLC肿瘤细胞中PD-L1表达是否与特定临床特征或总生存期相关。
一项回顾性研究纳入了482例患者经福尔马林固定石蜡包埋（FFPE）的手术肿瘤样本。使用克隆28-8、22C3、SP263和SP142通过免疫组织化学在组织微阵列上的肿瘤细胞中评估PD-L1状态。通过Kaplan-Meier法和多变量Cox回归分析评估与总生存期的相关性。患者的中位年龄为68岁（39-86岁）；组织学类型：腺癌（AdCa）61%，鳞状细胞癌（SqCC）33%，大细胞癌（LCC）6%；p分期：IA期（46%），IB期（30%），IIA期（10%），IIB期（11.4%），IIIA期（1.2%），IIIB-IV期（0.4%）。NSCLC中克隆28-8、22C3、SP263、SP142的PD-L1阳性率（≥1%）分别为41.5%、34.2%、42.7%、10.4%（Pearson卡方检验p<0.0001）。PD-L1表达与组织学类型、肿瘤大小和分级相关。使用克隆SP142观察到NSCLC和非腺癌中PD-L1表达与总生存期之间具有统计学意义的关联（对数秩检验p分别为0.045和0.05）。使用克隆22C3（对数秩检验p=0.009）和SP263（对数秩检验p=0.050）观察到LCC中PD-L1表达与总生存期之间具有统计学意义的关联。
PD-L1克隆SP142的过表达与NSCLC和非腺癌的总生存期较差相关。克隆22C3和SP263与LCC的预后较差相关。PD-L1状态可能作为NSCLC的预后标志物。
