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

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.