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

¹Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
²Department of Hospital Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
³Department of Diagnostic Pathology and Cytology, Kuma Hospital, Kobe, Japan.
⁴Department of Surgery, Kuma Hospital, Kobe, Japan.
⁵Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁶Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁸Precision Pathology of Neoplasia Research Group, Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
⁹Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
¹⁰Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea.
¹¹Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
¹²Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹³Department of Endocrine Surgery, Yamashita Thyroid and Parathyroid Clinic, Fukuoka, Japan.
¹⁴Department of Tumor and Diagnostic Pathology, Nagasaki University, Nagasaki, Japan.
¹⁵Department of Pathology, Izumi City General Hospital, Izumi, Japan.
¹⁶Department of Pathology, Kameda Medical Center, Kamogawa, Chiba, Japan.

⁰Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

The American Journal of Surgical Pathology +

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July 15, 2024

View abstract on PubMed

Summary

Most anaplastic thyroid carcinomas (ATCs) express PD-L1, a marker for immunotherapy response. PD-L1 expression varied by histology and was often higher in ATC than in co-existing differentiated thyroid carcinoma (DTC).

Area Of Science

Oncology
Immunotherapy
Thyroid Cancer Research

Background

Anti-programmed death (PD) immunotherapy is under investigation for anaplastic thyroid carcinoma (ATC).
Tumor cell surface PD-L1 expression is a predictive biomarker for anti-PD immunotherapy response.
Limited data exist on PD-L1 expression in ATC, unlike the more studied papillary thyroid carcinoma.

Purpose Of The Study

To assess PD-L1 expression in a large cohort of anaplastic thyroid carcinomas (ATCs).
To compare PD-L1 expression with histological patterns, specimen type, molecular profile, and patient outcomes.
To evaluate PD-L1 expression in co-existent differentiated thyroid carcinoma (DTC) and compare it with ATC.

Main Methods

Retrospective multi-institutional study involving 179 ATCs across 9 Asian centers.
PD-L1 expression assessed using the SP263 (Ventana) clone, with PD-L1 positivity defined as a tumor proportion score (TPS) ≥1%.
Analysis included comparison with histological patterns, specimen size, BRAF V600E and TERT promoter mutation status, and patient outcomes.

Main Results

73.2% of ATCs were PD-L1-positive, with a median TPS of 36% among positive cases.
PD-L1-negative cases were more frequent in small specimens; epithelioid and pleomorphic ATCs showed higher PD-L1 expression than sarcomatoid types.
PD-L1 expression was frequently converted from DTC-negative to ATC-positive (71% of cases); BRAF V600E mutation correlated with PD-L1 positivity.

Conclusions

The majority of ATCs exhibit PD-L1 expression, suggesting potential benefit from anti-PD immunotherapy.
PD-L1 expression patterns differ between ATC and DTC, with a notable conversion in co-existing tumors.
BRAF V600E mutation status may inform combination therapy strategies with anti-PD agents, although PD-L1 expression did not impact overall patient outcome.

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