Prognostic Characterization of Papillary Thyroid Carcinoma: Insights into the Role of PD-L1 and Mutational Landscape in Disease Aggressiveness and Outcome

Background: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, with generally favorable outcomes. However, a subset of patients experiences aggressive disease progression, recurrence, and metastasis, necessitating refined prognostic tools. This study investigates the prognostic significance of PD-L1 expression, measured by the Tumor Proportion Score (TPS), in conjunction with genetic mutations (BRAF, TERT, RAS) and clinicopathological features in PTC. Methods: A retrospective analysis was conducted on 84 PTC patients diagnosed between July 2016 and June 2024 at King George’s Medical University, India. Formalin-fixed paraffin-embedded (FFPE) tissues were evaluated for PD-L1 expression using immunohistochemistry (IHC), with TPS categorized as low or high based on median values. Molecular analysis identified BRAF, TERT, and RAS mutations. Clinicopathological data, including tumor size, lymph node involvement, extrathyroidal extension, and recurrence, were collected. Statistical analyses assessed associations between TPS, molecular markers, and clinical outcomes. Results: PD-L1 expression was observed in 60.7% of cases, with 38.1% classified as TPS high. PD-L1 high was significantly associated with older age, advanced tumour stage, lymph node involvement, and aggressive histological variants (p < 0.05). BRAF and TERT mutations were more prevalent in PD-L1 high cases (p = 0.032 and p = 0.038, respectively). PD-L1 high correlated with increased recurrence (p = 0.043) and distant metastasis (p = 0.002). Multivariable analysis identified multiple mutations as independent predictors of poor survival (AOR = 15.8, p = 0.021) and recurrence (AOR = 11.22, p < 0.001). Conclusion: PD-L1 expression, particularly when combined with BRAF and TERT mutations, serves as a valuable prognostic marker in PTC. PD-L1 high is associated with aggressive tumour behaviour, recurrence, and metastasis, highlighting its potential for risk stratification and personalized treatment strategies. Further prospective studies are needed to validate these findings and explore the therapeutic implications of PD-L1 in PTC.