Anti-PD immunotherapy is currently under investigation in anaplastic thyroid carcinoma (ATC). Tumor cell surface PD-L1 expression is considered predictive of therapeutic response. Although papillary thyroid carcinoma has been widely studied for PD-L1 expression, there are limited data on ATC. In this retrospective multi-institutional study involving 9 centers across Asia, 179 ATCs were assessed for PD-L1 expression using the SP263 (Ventana) clone. A tumor proportion score (TPS) ≥1% was required to consider a case PD-L1-positive. PD-L1 expression was compared with the histological patterns, the type of specimen (small or large), tumor molecular profile (BRAF V600E and TERT promoter mutation status), and patient outcome. PD-L1 expression in any co-existent differentiated thyroid carcinoma (DTC) was evaluated separately and compared with ATC. Most ATCs (73.2%) were PD-L1-positive. The median TPS among positive cases was 36% (IQR 11% to 75%; range 1% to 99%). A high expression (TPS ≥ 50%) was noted in 30.7%. PD-L1-negative cases were more likely to be small specimens (P=0.01). A negative result on small samples, hence, may not preclude expression elsewhere. ATCs having epithelioid and pleomorphic histological patterns were more likely to be PD-L1-positive with higher TPS than sarcomatoid (P<0.01). DTCs were more frequently negative and had lower TPS than ATC (P<0.01). Such PD-L1 conversion from DTC-negative to ATC-positive was documented in 71% of cases with co-existent DTC. BRAF V600E, but not TERT promoter mutations, correlated significantly with PD-L1-positivity rate (P=0.039), reinforcing the potential of combining anti-PD and anti-BRAF V600E drugs. PD-L1 expression, however, did not impact the patient outcome.

中文翻译：

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PD-L1 在甲状腺间变性癌中的表达及其调节因子：一项多机构研究。


目前正在研究甲状腺未分化癌 （ATC） 的抗 PD 免疫疗法。肿瘤细胞表面 PD-L1 表达被认为可预测治疗反应。尽管甲状腺状癌的 PD-L1 表达已被广泛研究，但关于 ATC 的数据有限。在这项涉及亚洲 9 个中心的回顾性多机构研究中，使用 SP263 （Ventana） 克隆评估了 179 例 ATC 的 PD-L1 表达。需要肿瘤比例评分 （TPS） ≥1% 才能考虑病例 PD-L1 阳性。将 PD-L1 表达与组织学模式、标本类型 （小或大） 、肿瘤分子谱 （BRAF V600E 和 TERT 启动子突变状态） 和患者结局进行比较。单独评估 PD-L1 在任何共存的分化型甲状腺癌 （DTC） 中的表达并与 ATC 进行比较。大多数 ATC （73.2%） 为 PD-L1 阳性。阳性病例的中位 TPS 为 36% （IQR 11% 至 75%;范围 1% 至 99%）。30.7% 的患者出现高表达 （TPS ≥ 50%）。PD-L1 阴性病例更可能是小标本 （P=0.01）。因此，小样品的阴性结果可能不排除其他位置的表达。与肉瘤样相比，具有上皮样和多形性组织学模式的 ATC 更可能为 PD-L1 阳性且 TPS 更高 （P<0.01）。DTCs 比 ATC 更常见于阴性且 TPS 更低 （P<0.01）。在 71% 共存 DTC 的病例中记录了这种从 DTC 阴性到 ATC 阳性的 PD-L1 转变。BRAF V600E 与 PD-L1 阳性率显著相关 （P=0.039），增强了联合抗 PD 和抗 BRAF V600E 药物的潜力。然而，PD-L1 表达不会影响患者的预后。