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PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma: A Multi-institutional Study.
The American Journal of Surgical Pathology ( IF 4.5 ) Pub Date : 2024-07-15 , DOI: 10.1097/pas.0000000000002284
Shipra Agarwal, Chan Kwon Jung, Pranitha Gaddam, Mitsuyoshi Hirokawa, Takuya Higashiyama, Jen-Fan Hang, Wei-An Lai, Somboon Keelawat, Zhiyan Liu, Hee Young Na, So Yeon Park, Junya Fukuoka, Shinya Satoh, Zhanna Mussazhanova, Masahiro Nakashima, Kennichi Kakudo, Andrey Bychkov

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:


甲状腺未分化癌中的 PD-L1 表达及其调节因子:一项多机构研究。



目前正在研究针对甲状腺未分化癌(ATC)的抗 PD 免疫疗法。肿瘤细胞表面 PD-L1 表达被认为可以预测治疗反应。尽管甲状腺乳头状癌的 PD-L1 表达已被广泛研究,但 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 个 ATC 的 PD-L1 表达。肿瘤比例评分 (TPS) ≥1% 需考虑 PD-L1 阳性病例。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)和患者结果进行比较。单独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%) 呈 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阴性病例更有可能是小样本(P=0.01)。因此,小样本的阴性结果可能不会排除其他地方的表达。具有上皮样和多形性组织学模式的 ATC 更有可能是 PD-L1 阳性,且 TPS 高于肉瘤样 (P<0.01)。与 ATC 相比,DTC 更频繁地呈阴性且 TPS 较低 (P<0.01)。 71% 的 DTC 共存病例中记录了这种 PD-L1 从 DTC 阴性到 ATC 阳性的转变。 BRAF V600E(而非 TERT 启动子突变)与 PD-L1 阳性率显着相关(P=0.039),增强了抗 PD 和抗 BRAF V600E 药物组合的潜力。然而,PD-L1 表达并不影响患者的治疗结果。
更新日期:2024-07-15
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