PD-L1 expression in rare and aggressive thyroid cancers: A preliminary investigation for a role of immunotherapy

Background and Aim: Programmed cell death ligand-1 (PD-L1) immunoexpression status determines the response to immunotherapy in many cancers. Limited data exist on PD-L1 status in aggressive thyroid tumors. We investigated PD-L1 expression across thyroid cancers and correlated it with their molecular profile. Materials and Methods: Sixty-five cases of differentiated thyroid carcinoma, poorly differentiated thyroid carcinoma (PDTC), and anaplastic thyroid carcinoma (ATC) were assessed for PD-L1 expression (clone SP263, VENTANA). The differentiated cases encompassed the aggressive hobnail and tall cell subtypes of papillary thyroid carcinoma (PTC) besides classical PTC and follicular thyroid carcinoma (FTC). Ten nodular goiters (NG) were also evaluated. Tumor proportion score (TPS) and H-score were calculated. BRAFV600E and H-/ K-/ N-RAS were assessed using allele-specific real-time polymerase chain reaction (PCR). Fisher's exact and Kruskal-Wallis tests were used to investigate the associations between the categorical variables and compare PD-L1 scores with the mutation status. Results: Most PTC (87%) and ATC (73%) cases were PD-L1 positive (TPS >= 1%), with significantly higher positivity rates than NG (20%). TPS >50% was seen in 60% ATC and 7% PTC cases. The median TPS and H-score of ATC were 56 (0-96.6) and 168 (0-275), respectively, and of PTC were 9.6 (4-16.8) and 17.8 (6.6-38.6), respectively. The scores were similar across the PTC subtypes. Only one case each of FTC and PDTC was PD-L1 positive. PD-L1 expression correlated significantly with BRAFV600E, but not with RAS mutation. Conclusions: ATC showed intense and diffuse PD-L1 staining. Although most PTCs were PD-L1 positive, the expression was weaker and patchy, irrespective of the histological subtype. Results of this pilot study indicate that ATC is most likely to respond to immunotherapy. PTC, FTC, and PDTC may be less amenable to immunotherapy. PD-L1 expression correlated significantly with BRAFV600E, allowing for combined targeted therapy.