Prognostic Value of Programmed Cell Death Ligand 1 (PD-L1) Expression in Patients With Papillary Thyroid Carcinoma: A Retrospective Biomarker Study.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) expression is a well-established prerequisite for the use of immune checkpoint inhibitors and is increasingly recognized as a prognostic biomarker in various malignancies. However, its prognostic significance in thyroid cancer, particularly papillary thyroid carcinoma (PTC), remains largely unexplored and somewhat controversial, with findings to date being limited and inconsistent. The aim of this study was to evaluate PD-L1 expression in a well-characterized cohort of patients with PTC and assess its association with key clinicopathological features and clinical outcomes. MATERIALS AND METHODS: This retrospective, single-center cohort study included patients with histologically confirmed PTC who underwent thyroid surgery at the Korgialenio-Benakio Hellenic Red Cross Hospital of Athens in Greece between 2007 and 2018. Formalin-fixed, paraffin-embedded tumor samples were assessed for PD-L1 expression using immunohistochemistry and scored using the combined positive score (CPS), with CPS ≥10 indicating PD-L1 positivity. Clinicopathological data were collected through review of patients' medical records and postoperative histopathology reports, and associations with PD-L1 status were analyzed. Disease-free survival (DFS) and overall survival (OS) were also evaluated using Kaplan-Meier methods. RESULTS: Among 81 patients with PTC included in this study (median age: 48 years, 61/81 (83%) patients being female), PD-L1 positivity (CPS ≥10) was observed in 37/81 (45.7%) patients. CPS ≥10 status was significantly associated with larger tumor size, higher pT stage (pT3-pT4, as per the 8th edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) classification), extrathyroidal extension, lymph node metastasis, and the presence of aggressive histologic variants. Coexisting Hashimoto's thyroiditis and higher rates of radioactive iodine therapy were also more common in the PD-L1-positive group. At a median follow-up of nine years, the overall recurrence rate was 8.6% (7/81 patients), with significantly higher recurrence and shorter DFS among patients with CPS ≥10. OS remained high across both groups. CONCLUSIONS: PD-L1 expression was present in nearly half of this real-world Greek PTC cohort and was associated with multiple adverse clinicopathological features and an increased risk of recurrence. These findings support the potential utility of PD-L1 as a prognostic biomarker in PTC and may inform postoperative risk stratification and follow-up strategies, although further prospective studies in larger, multicenter cohorts are warranted to corroborate these results.