Roper Edward, Lum Trina, Palme Carsten E, Ashford Bruce, Ch'ng Sydney, Ranson Marie, Boyer Michael, Clark Jonathan, Gupta Ruta
Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, Australia.
Sydney Head and Neck Cancer Institute, Chris O'Brien Lifehouse, Sydney, Australia; Central Clinical School, University of Sydney, Sydney, Australia.
Pathology. 2017 Aug;49(5):499-505. doi: 10.1016/j.pathol.2017.04.004. Epub 2017 Jun 27.
Programmed cell death (PD-1) and its ligand (PD-L1) inhibitors have shown clinical response in many tumours. PD-L1 data are limited in head and neck cutaneous squamous cell carcinoma (HNcSCC) and no clinical trials of PD-1/PD-L1 inhibitors are published. We performed PD-L1 immunohistochemistry on 74 cases of high risk HNcSCC with 38 matched metastases and evaluated clinicopathological associations, prognostic significance and heterogeneity in matched metastases. We observed PD-L1 expression in >5% of primary tumour cells in 29 cases (39.2%), primary tumour infiltrating lymphocytes (TILs) in 40 cases (70.2%), metastatic tumour cells in 15 cases (39.5%), and metastatic TILs in 18 cases (47.4%). PD-L1 expression in >5% of primary tumour cells was associated with an inflammatory phenotype (p = 0.04), and in primary TILs with clear margins (p = 0.05). PD-L1 expression in >5% of primary tumour cells (p = 0.01), primary TILs (p = 0.001), and metastatic TILs (p = 0.02) was associated with improved disease free survival. PD-L1 expression in >5% of tumour cells was heterogeneous between primary and metastatic tumours in 13 cases (34.2%). PD-L1 expression is common in HNcSCC supporting the rationale for a clinical trial of PD-1/PD-L1 inhibitors. PD-L1 expression in tumour cells or TILs predicts longer disease free survival and demonstrates temperospatial heterogeneity.
程序性细胞死亡蛋白1(PD - 1)及其配体(PD - L1)抑制剂已在多种肿瘤中显示出临床疗效。在头颈部皮肤鳞状细胞癌(HNcSCC)中,PD - L1的数据有限,且尚无关于PD - 1/PD - L1抑制剂的临床试验发表。我们对74例高危HNcSCC患者及38例配对转移灶进行了PD - L1免疫组化分析,评估了临床病理相关性、预后意义及配对转移灶中的异质性。我们观察到,29例(39.2%)原发性肿瘤细胞中PD - L1表达>5%,40例(70.2%)原发性肿瘤浸润淋巴细胞(TILs)中表达>5%,15例(39.5%)转移瘤细胞中表达>5%,18例(47.4%)转移TILs中表达>5%。原发性肿瘤细胞中PD - L1表达>5%与炎症表型相关(p = 0.04),原发性TILs中表达>5%且边界清晰与炎症表型相关(p = 0.05)。原发性肿瘤细胞中PD - L1表达>5%(p = 0.01)、原发性TILs中表达>5%(p = 0.001)以及转移TILs中表达>5%(p = 0.02)与无病生存期延长相关。13例(34.2%)患者的原发性肿瘤和转移瘤中,肿瘤细胞中PD - L1表达>5%的情况存在异质性。PD - L1表达在HNcSCC中很常见,这为PD - 1/PD - L1抑制剂的临床试验提供了理论依据。肿瘤细胞或TILs中的PD - L1表达预示着更长的无病生存期,并显示出时空异质性。