Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2024 Oct 1;48(10):1233-1244.
doi: 10.1097/PAS.0000000000002284. Epub 2024 Jul 15.

PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma: A Multi-institutional Study

Shipra Agarwal  1 , Chan Kwon Jung  2 , Pranitha Gaddam  1 , Mitsuyoshi Hirokawa  3 , Takuya Higashiyama  4 , Jen-Fan Hang  5 , Wei-An Lai  6 , Somboon Keelawat  7   8 , Zhiyan Liu  9 , Hee Young Na  10   11 , So Yeon Park  10   11 , Junya Fukuoka  12 , Shinya Satoh  13 , Zhanna Mussazhanova  14 , Masahiro Nakashima  14 , Kennichi Kakudo  15 , Andrey Bychkov  16
Affiliations
Multicenter Study

PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma: A Multi-institutional Study

Shipra Agarwal et al. Am J Surg Pathol. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. This research was supported by the following grants/funds/programs: grant (HI21C0940) from the Korean Health Technology R&D Project funded by the Ministry of Health and Welfare, Republic of Korea to C.K.J.; funding received from the Indian Council of Medical Research, New Delhi, India (Order No. 52/29/2020-Bio/BMS) to S.A.; the Atomic Bomb Disease Institute, Nagasaki University; and the Program of the Network-Type Joint Usage/Research Center for Radiation Disaster Medical Science to M.N.

Similar articles

See all similar articles

Cited by

References

    1. Molinaro E, Romei C, Biagini A, et al. Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol. 2017;13:644–660.
    1. Bible KC, Kebebew E, Brierley J, et al. 2021 American Thyroid Association Guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2021;31:337–386.
    1. Agarwal S, Bychkov A, Jung CK. Emerging biomarkers in thyroid practice and research. Cancers (Basel). 2021;14:204.
    1. Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl Med. 2016;8:328rv4.
    1. Marcus L, Fashoyin-Aje LA, Donoghue M, et al. FDA approval summary: pembrolizumab for the treatment of tumor mutational burden-high solid tumors. Clin Cancer Res. 2021;27:4685–4689.

Publication types

MeSH terms