Prognostic characterization of papillary thyroid carcinoma: Insights into the role of PD-L1 and mutational landscape in disease aggressiveness and outcome.

Abstract

Objectives: Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer, generally associated with an excellent prognosis. However, a subset of tumors behaves aggressively, highlighting the need for reliable prognostic biomarkers to improve risk stratification beyond traditional clinicopathologic parameters. This study evaluates the prognostic value of PD-L1 expression and its association with key molecular alterations in PTC.

Methods: This retrospective study included 84 patients with PTC treated at King George's Medical University between 2016 and 2024. PD-L1 expression was assessed using the tumor proportion score. Correlations with clinicopathologic features, BRAF and TERT promoter mutations, recurrence, and survival outcomes were analyzed. Multivariable analysis was performed to identify independent prognostic factors.

Results: PD-L1 expression was positive in 60.7% of cases, with 38.1% classified as high expressors. High PD-L1 expression was significantly associated with advanced tumor stage, lymph node metastasis, aggressive histologic variants, and absence of thyroiditis. PD-L1 upregulation correlated strongly with BRAF and TERT promoter mutations. Coexisting BRAF and TERT mutations emerged as independent predictors of recurrence and poor survival. Clinically, recurrence occurred in 20.2% of patients and metastasis in 8.3%, both significantly associated with high PD-L1 expression. Multivariable analysis confirmed multiple mutations and PD-L1 overexpression as key prognostic factors.

Conclusions: PD-L1 is a robust biomarker of aggressiveness in PTC. Integrating PD-L1 testing with molecular profiling can enhance postoperative risk stratification and guide personalized management.