Ahn Soomin, Kim Tae Hyuk, Kim Sun Wook, Ki Chang Seok, Jang Hye Won, Kim Jee Soo, Kim Jung Han, Choe Jun-Ho, Shin Jung Hee, Hahn Soo Yeon, Oh Young Lyun, Chung Jae Hoon
Department of PathologyEwha Womans University School of Medicine, Seoul, Korea.
Division of Endocrinology and MetabolismDepartment of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Endocr Relat Cancer. 2017 Feb;24(2):97-106. doi: 10.1530/ERC-16-0421.
PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various thyroid cancers on a large scale. A total of 407 primary thyroid cancers with a median 13.7-year of follow-up were included. We evaluated the frequency of PD-L1 expression using a rabbit monoclonal antibody (clone SP142). In addition, we analyzed the relationships between PD-L1 expression and clinicopathologic factors, including TERT promoter, BRAF status and disease progression. Tumoral PD-L1 was expressed in 6.1% of papillary thyroid carcinomas, 7.6% of follicular thyroid carcinomas and 22.2% of anaplastic thyroid carcinomas. The distribution of PD-L1 positivity was different according to cancer histology types (P < 0.001). All PD-L1-positive cases of follicular thyroid carcinoma and anaplastic thyroid carcinoma showed strong intensity. The proportions of positivity in PD-L1 positive anaplastic thyroid carcinomas were more than 80%. PD-L1 in immune cells was positive in 28.5% of papillary thyroid carcinoma, 9.1% of follicular thyroid carcinomas and 11.1% of anaplastic thyroid carcinomas. There was no significant association between clinicopathologic variables, disease progression, oncogenic mutation and PD-L1 expression. PD-L1 was highly expressed in a subset of patients with advanced thyroid cancer, such as follicular and anaplastic thyroid carcinoma. Identification of PD-L1 expression may have direct therapeutic relevance to patients with refractory thyroid cancer.
PD-L1表达正被视为各种肿瘤中抗PD-1或抗PD-L1药物反应的潜在生物标志物。甲状腺癌中报道的PD-L1阳性频率各不相同,多种因素可能导致PD-L1阳性的变异性。我们大规模评估了各种甲状腺癌中的PD-L1表达。共纳入407例原发性甲状腺癌,中位随访时间为13.7年。我们使用兔单克隆抗体(克隆号SP142)评估PD-L1表达频率。此外,我们分析了PD-L1表达与临床病理因素之间的关系,包括TERT启动子、BRAF状态和疾病进展。肿瘤性PD-L1在6.1%的乳头状甲状腺癌、7.6%的滤泡状甲状腺癌和22.2%的间变性甲状腺癌中表达。根据癌症组织学类型,PD-L1阳性的分布不同(P<0.001)。所有滤泡状甲状腺癌和间变性甲状腺癌的PD-L1阳性病例均显示强阳性强度。间变性甲状腺癌PD-L1阳性病例中的阳性比例超过80%。免疫细胞中的PD-L1在28.5%的乳头状甲状腺癌、9.1%的滤泡状甲状腺癌和11.1%的间变性甲状腺癌中呈阳性。临床病理变量、疾病进展、致癌突变与PD-L1表达之间无显著关联。PD-L1在晚期甲状腺癌患者的一个亚组中高表达,如滤泡状和间变性甲状腺癌。PD-L1表达的鉴定可能与难治性甲状腺癌患者的直接治疗相关。