Nodal Metastases Associated With Fusion Oncogenes Are Age Dependent in Young Adult Patients With Thyroid Cancer.

Context: Fusion oncogenes, especially those involving RET or NTRK, are known drivers of papillary thyroid cancer (PTC). They are prevalent in pediatric patients and correlate with aggressive tumor behavior.

Objective: We explored the age dependence of fusion oncogenes and aggressive tumor behavior in young adult PTC patients.

Experimental Design: We examined 150 tumors from 142 PTC patients aged between 17∼35 years old with established tumor-node-metastasis stages. Oncogenic drivers and the thyroid differentiation score (TDS) were determined by DNA and RNA sequencing of a target panel. Transcriptome analysis was performed in PTCs with RET fusions.

Results: Among 150 PTCs, we detected BRAF V600E (n = 105), RET fusions (n = 15), NTRK3 fusions (n = 8), and BRAF fusions (n = 4). We found that fusion oncogenes were associated with nodal metastasis when age was tiered into 3 groups: <25 years, 25∼29 years, and 30∼35 years. Patients under 25 years old showed a marginal increase in tumor stage compared to those over 25 years (75.00% vs 21.74%, P = .0646). Risk of lateral lymph node metastasis increased with younger age (75.00% vs 27.27% vs 8.33%, P = .0369). As with advanced tumor and node stage, patients harboring fusion oncogenes and aged under 25 years showed the lowest TDS; genes associated with immunoglobulin production and production of molecular mediators of the immune response were significantly upregulated.

Conclusions: Adult PTC patients under 25 years with fusion oncogenes showed a tendency toward advanced tumor stage and lower thyroid differentiation. Integrating onset age together with oncogenic alterations is worthwhile when managing adult PTC patients.