Clinicopathological Characteristics and Prognostic Significance of <scp>RET</scp> Fusion in Papillary Thyroid Carcinoma

BACKGROUND: To analyze the clinicopathological features and long-term outcomes of papillary thyroid carcinoma (PTC) patients with rearranged during transfection (RET) proto-oncogene fusion positive and to explore their genotype-phenotype associations and prognostic significance. METHODS: A retrospective study was conducted on 828 PTC patients treated at Sun Yat-sen University Cancer Center between January 2018 and December 2020. RET fusions, as well as BRAF and TERT promoter mutations, were primarily detected by quantitative real-time polymerase chain reaction. Demographic, clinicopathological, and follow-up data were obtained and analyzed to identify genotype-specific disease patterns. RESULTS: RET fusions were identified in 64 patients (7.7%). RET fusion-positive patients had a significantly greater proportion of pediatric and adolescent onset (12.5% vs. 0.7%; p < 0.001) and had larger tumors (34.4% vs. 10.1%, p < 0.001), higher rates of lateral cervical lymph node metastasis (64.1% vs. 24.6%, p < 0.001), distant metastasis (14.1% vs. 1.0%, p < 0.001), extrathyroidal extension (23.4% vs. 13.9%, p = 0.037), vascular invasion (17.2% vs. 3.9%, p < 0.001), perineural invasion (17.2% vs. 4.6%, p < 0.001), and extranodal extension (34.4% vs. 4.8%, p < 0.001) than their RET fusion-negative counterparts. The follow-up data indicated a higher rate of disease progression and poorer clinical outcomes in RET fusion-positive patients than in RET fusion-negative patients (21.9% vs. 2.6%, p < 0.001). CONCLUSIONS: RET fusion-positive PTC is associated with aggressive clinicopathological behavior and poor prognosis. This study highlights the importance of RET fusion testing in PTC for more accurate risk stratification and personalized therapeutic approaches, particularly for high-risk patients.