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Medullary Thyroid Carcinoma in MEN2A: ATA Moderate- or High-Risk RET Mutations Do Not Predict Disease Aggressiveness

2017; Oxford University Press; Volume: 102; Issue: 8 Linguagem: Inglês

10.1210/jc.2017-00317

1945-7197

Rachel K. Voss, Lei Feng, Jeffrey E. Lee, Nancy D. Perrier, Paul H. Graham, Samuel M. Hyde, Frances Nieves-Munoz, Maria E. Cabanillas, Steven G. Waguespack, Gilbert J. Cote, Robert F. Gagel, Elizabeth G. Grubbs,

BRCA gene mutations in cancer

High-risk RET mutations (codon 634) are associated with earlier development of medullary thyroid carcinoma (MTC) and presumed increased aggressiveness compared with moderate-risk RET mutations.To determine whether high-risk RET mutations are more aggressive.Retrospective cohort study using institutional multiple endocrine neoplasia type 2 registry.Tertiary cancer care center.Patients with MTC and moderate- or high-risk germline RET mutation.None (observational study).Proxies for aggressiveness were overall survival (OS) and time to distant metastatic disease (DMD).A total of 127 moderate-risk and 135 high-risk patients were included (n = 262). Median age at diagnosis was 42.3 years (range, 6.4 to 86.4 years; mean, 41.6 years) for moderate-risk mutations and 23.0 years (range, 3.7 to 66.8 years; mean, 25.6 years) for high-risk mutations (P < 0.0001). Moderate-risk patients had more T3/T4 tumors at diagnosis (P = 0.03), but there was no significant difference for N or M stage and no significant difference in OS (P = 0.40). From multivariable analysis for OS, increasing age [hazard ratio (HR), 1.05/y; 95% confidence interval (CI), 1.03 to 1.08], T3/T4 tumor (HR, 2.73; 95% CI, 1.22 to 6.11), and M1 status at diagnosis (HR, 3.93; 95% CI, 1.61 to 9.59) were significantly associated with worse OS but high-risk mutation was not (P = 0.40). No significant difference was observed for development of DMD (P = 0.33). From multivariable analysis for DMD, only N1 status at diagnosis was significant (HR, 2.10; 95% CI, 1.03 to 4.27).Patients with high- and moderate-risk RET mutations had similar OS and development of DMD after MTC diagnosis and therefore similarly aggressive clinical courses. High-risk connotes increased disease aggressiveness; thus, future guidelines should consider RET mutation classification by disease onset (early vs late) rather than by risk (high vs moderate).