PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma

Author:

Agarwal Shipra1,Jung Chan Kwon2,Gaddam Pranitha1,Hirokawa Mitsuyoshi3,Higashiyama Takuya4,Hang Jen-Fan5,Lai Wei-An6,Keelawat Somboon78,Liu Zhiyan9,Na Hee Young1011,Park So Yeon1011,Fukuoka Junya12,Satoh Shinya13,Mussazhanova Zhanna14,Nakashima Masahiro14,Kakudo Kennichi15,Bychkov Andrey16

Affiliation:

1. Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

2. Department of Hospital Pathology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea

3. Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan

4. Department of Surgery, Kuma Hospital, Kobe, Japan

5. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

6. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

7. Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

8. Precision Pathology of Neoplasia Research Group, Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

9. Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

10. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea

11. Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea

12. Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

13. Department of Endocrine Surgery, Yamashita Thyroid and Parathyroid Clinic, Fukuoka, Japan

14. Department of Tumor and Diagnostic Pathology, Nagasaki University, Nagasaki, Japan

15. Department of Pathology, Izumi City General Hospital, Izumi, Japan

16. Department of Pathology, Kameda Medical Center, Kamogawa, Chiba, Japan

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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