Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Department of Hospital Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
Am J Surg Pathol. 2024 Oct 1;48(10):1233-1244. doi: 10.1097/PAS.0000000000002284. Epub 2024 Jul 15.
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.
抗 PD 免疫疗法目前正在进行间变性甲状腺癌（ATC）的研究。肿瘤细胞表面 PD-L1 的表达被认为是治疗反应的预测指标。尽管甲状腺乳头状癌的 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 个中心的回顾性多中心研究中，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%才能认为病例 PD-L1 阳性。将 PD-L1 表达与组织学模式、标本类型（小标本或大标本）、肿瘤分子特征（BRAF V600E 和 TERT 启动子突变状态）以及患者预后进行比较。分别评估任何共存的分化型甲状腺癌（DTC）中的 PD-L1 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%）。高表达（TPS≥50%）占 30.7%。PD-L1 阴性病例更可能为小标本（P=0.01）。因此，小样本的阴性结果可能并不排除其他部位的表达。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 较高，而肉瘤样者则较低（P<0.01）。DTC 比 ATC 更常见且 TPS 更低（P<0.01）。在 71%的共存 DTC 病例中记录了从 DTC 阴性到 ATC 阳性的 PD-L1 转换。BRAF V600E，但不是 TERT 启动子突变，与 PD-L1 阳性率显著相关（P=0.039），这强化了联合使用抗 PD 和抗 BRAF V600E 药物的潜力。然而，PD-L1 表达并未影响患者预后。
