评估低分化、高分化甲状腺癌及甲状腺未分化癌中PD-L1、TERT启动子突变和BRAFV600E突变：我们机构的经验

Evaluation of PD-L1, TERT promoter mutations, and BRAFV600E mutation in poorly differentiated, differentiated high grade thyroid carcinoma and anaplastic carcinoma of the thyroid: our institutional experience.

作者信息

Piermattei Alessia, Migliara Giuseppe, Feraco Angela, Bruno Carmine, Cioni Luisa, Zhang Qianqian, Padial-Urtueta Belen, Merenda Elisabetta, Fadda Guido, Raffaelli Marco, Larocca Luigi Maria, Mule Antonino, Pontecorvi Alfredo, Rossi Esther Diana

机构信息

Division of Anatomic Pathology and Histology Fondazione, Policlinico Universitario"Agostino Gemelli"-IRCCS, Rome, Italy.

Dipartimento Di Sanita' Pubblica E Malattie Infettive, Univerista' La Sapienza, Rome, Italy.

出版信息

Virchows Arch. 2025 Jun 7. doi: 10.1007/s00428-025-04134-1.

DOI:10.1007/s00428-025-04134-1

PMID:40481961

Abstract

Although many thyroid cancers are well-differentiated carcinomas with an indolent behavior, poorly differentiated (PDTC) and anaplastic thyroid carcinomas (ATC) represent a minority of thyroid malignancies with an aggressive and/or lethal course, followed by limited effective treatment options. Recently, the WHO 2022 introduced the concept of high-grade follicular cell-derived malignancy, including both the traditional PDTC as well as the new definition of high-grade differentiated thyroid carcinomas (DHGTC). Both are characterized by increased mitotic activity and tumor necrosis without anaplastic features and similar clinical behavior. In the last years, immune checkpoint inhibitors (ICIs) have shown to be an effective treatment for a variety of carcinomas, especially aggressive types such as PDTC and ATC, with less data available about DHGTC. The current study analyzes a cohort of patients with PDTC, DHGTC and ATC focusing on the expression of programmed cell death-ligand 1 (PD-L1) and BRAFV600E correlated with aggressive features. From January 2010 to December 2023, 73 patients including a diagnosis of PDTC, DHGTC, and ATC were diagnosed. All these cases were analyzed for the PD-L1 expression and BRAFV600E and correlated with the clinic-pathological features. Among the 73 cases, 42 (57.5%) were women. The median age was 64.2 years. Histological diagnoses included 35 (38.4%) PDTC, 8 DHGTC, and 30 (46.1%) ATC. Lymph-nodal involvement was seen in 27 cases (including 12 N1a, and 15 N1b), while vascular invasion in 34 cases. A differentiated component was seen in all DHGTC, 5PDTC, 11 ATC. Evaluating the stage, 60 cases were from pT3a to pT4b. PD-L1 was expressed in 24/73 (5DHGTC, 0 PDTC, 19 ATC); BRAFV600E and TERT were positive in 19 cases and 16 cases respectively. PD-L1 was confirmed to be a potential biomarker for the management of patients with DHGTC and ATC. Although it did not yield a prognostic role in PDTC and ATC, it is likely to define a subset of patients directed to the checkpoint inhibitor therapy. Furthermore, TERT mutations showed a strong correlation with overall survival rate.

摘要

尽管许多甲状腺癌是具有惰性生物学行为的高分化癌，但低分化（PDTC）和未分化甲状腺癌（ATC）在甲状腺恶性肿瘤中占少数，具有侵袭性和/或致死性病程，且有效治疗选择有限。最近，2022年世界卫生组织引入了高级别滤泡细胞源性恶性肿瘤的概念，包括传统的PDTC以及高级别分化型甲状腺癌（DHGTC）的新定义。两者均以有丝分裂活性增加和肿瘤坏死为特征，无未分化特征且临床行为相似。在过去几年中，免疫检查点抑制剂（ICIs）已被证明是治疗多种癌症的有效方法，尤其是PDTC和ATC等侵袭性类型，而关于DHGTC的数据较少。本研究分析了一组PDTC、DHGTC和ATC患者，重点关注程序性细胞死亡配体1（PD-L1）和BRAFV600E的表达与侵袭性特征的相关性。2010年1月至2023年12月，共诊断出73例包括PDTC、DHGTC和ATC的患者。对所有这些病例进行了PD-L1表达、BRAFV600E分析，并与临床病理特征相关联。73例病例中，42例（57.5%）为女性。中位年龄为64.2岁。组织学诊断包括35例（38.4%）PDTC、8例DHGTC和30例（46.1%）ATC。27例出现淋巴结受累（包括12例N1a和15例N1b），34例出现血管侵犯。所有DHGTC、5例PDTC、11例ATC中可见分化成分。评估分期，60例为pT3a至pT4b。24/73（5例DHGTC、0例PDTC、19例ATC）表达PD-L1；BRAFV600E和TERT分别在19例和16例中呈阳性。PD-L1被证实是管理DHGTC和ATC患者的潜在生物标志物。尽管它在PDTC和ATC中未产生预后作用，但可能确定一部分适合接受检查点抑制剂治疗的患者。此外，TERT突变与总生存率显示出强烈相关性。