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

Abstract

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.

Update on current diagnosis and management of anaplastic thyroid carcinoma

“…Blocking this protein may increase the action of BRAF-V600E gene inhibitors, thus preventing the progression of the mutated malignancy[ 51 ]. PD-L1 expression was found to be positive in a high proportion in papillary 87% but with weaker and patchy expression, and in anaplastic thyroid carcinoma 73%, indicating that the latter can exhibit a better response to immunotherapy[ 59 ].…”

Harnessing Immunity to Treat Advanced Thyroid Cancer

“…In DTC, the positivity of PD-L1 varied among studies. Although two studies focusing on PTC reported low PD-L1 positivity rates, ranging from 6.1 to 10.1% [ 53 , 84 ], other studies reported higher PD-L1 positivity rates, ranging from 0.3 to 87% [ 47 , 85 , 86 ]. It should be noted that the expression of PD-L1 is significantly higher in aggressive PTC than in non-aggressive PTC [ 85 ].…”

“…PD-L1 expression is relatively low, with positivity rates ranging from 12.5 to 14.4% in MTC [ 88 , 89 ]. In ATC, the expression of PD-L1 is relatively high, ranging from 60 to 81.3% [ 53 , 86 , 90 , 91 ]. A direct comparison between histological types has shown that higher expression of PD-L1 is observed in ATC than in DTC [ 84 , 86 ].…”

“…In ATC, the expression of PD-L1 is relatively high, ranging from 60 to 81.3% [ 53 , 86 , 90 , 91 ]. A direct comparison between histological types has shown that higher expression of PD-L1 is observed in ATC than in DTC [ 84 , 86 ]. PD-L1 is diffusely expressed in ATC, whereas it is localized in PTC [ 84 ].…”

“…The BRAF V600E mutation activates MAPK signaling and is associated with poor outcomes and high recurrence rates [ 121 , 124 ]. Furthermore, 10–50% of patients with ATC carry the BRAF V600E mutation, which is associated with a poor prognosis [ 86 , 125 , 126 , 127 ]. Mutations or overexpression of the RAS gene family, including HRAS , KRAS , and NRAS , are observed in 20–30% of TC.…”