RET Fusion-Positive Papillary Thyroid Cancers are Associated with a More Aggressive Phenotype. Academic Article uri icon

Overview

abstract

  • BACKGROUND: It is unclear if different genetic drivers in papillary thyroid cancer (PTC) confer different phenotypic tumor behavior leading to more aggressive disease. We hypothesized that RET-driven cancers are more aggressive. PATIENTS AND METHODS: We reviewed records of consecutive patients treated for newly diagnosed PTC at this single institution from 2015 to 2016. Tumor samples from these patients were genotyped to identify RET-translocated, BRAFV600E mutant, and HRAS, KRAS, and NRAS mutant tumors. Patient demographic, clinicopathologic, and outcomes data were compared to identify genotype-specific patterns of disease. RESULTS: Of the 327 patients who underwent initial surgery for PTC during the study period, 192 (58.7%) had BRAFV600E mutant tumors (BRAF), 14 (4.3%) had RET-rearranged tumors (RET), 46 (14.1%) had RAS mutant tumors (RAS), and 75 (22.9%) had BRAF, RET, and RAS wildtype tumors. RET-driven tumors were more likely to have extrathyroidal extension (50.0% versus 27.0% for BRAF and 2.2% for RAS, P < 0.001), multifocal disease (85.7% versus 60.3%, and 44.4%, respectively, P = 0.017), and distant metastases (14.3% versus 1.1%, and 0%, respectively, P = 0.019). RET and BRAF patients also had worse disease-free survival than RAS patients (Kaplan-Meier log rank, P = 0.027). CONCLUSIONS: Patients with RET-driven PTCs had higher rates of extrathyroidal extension, multifocal disease, and distant metastases than patients whose tumors had BRAFV600E or RAS mutations. Patients with RET-rearranged tumors had similar disease-free survival to patients with BRAFV600E mutant tumors. RET rearrangement may confer an aggressive phenotype in PTC.

publication date

  • March 1, 2022

Identity

Scopus Document Identifier

  • 85054935868

Digital Object Identifier (DOI)

  • 10.1093/annonc/mdy137

PubMed ID

  • 35230579

Additional Document Info