RET Fusion-Positive Papillary Thyroid Cancers are Associated with a More Aggressive Phenotype.

TitleRET Fusion-Positive Papillary Thyroid Cancers are Associated with a More Aggressive Phenotype.
Publication TypeJournal Article
Year of Publication2022
AuthorsUllmann TM, Thiesmeyer JW, Lee YJoo, Beg S, Mosquera JMiguel, Elemento O, Fahey TJ, Scognamiglio T, Houvras Y
JournalAnn Surg Oncol
Date Published2022 Mar 01
ISSN1534-4681
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.

DOI10.1245/s10434-022-11418-2
Alternate JournalAnn Surg Oncol
PubMed ID35230579
PubMed Central ID3443896
Related Faculty: 
Juan Miguel Mosquera, M.D. Theresa Scognamiglio, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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