Do Prognostic Differences Exist Among High-Risk RET Mutations? A Comparison of Outcomes Between the RET C634R and Other C634 Mutations in Hereditary Medullary Thyroid Carcinoma
Authors' conclusion
Prognosis varied in hereditary MTC patients with RET C634 mutations. Our data highlight that the RET C634R mutation was associated with greater tumor aggressiveness in MTC and a poorer disease-specific survival.
Study context
- Population
- Patients with hereditary medullary thyroid carcinoma (MTC) carrying RET codon 634 mutations, 137 families, three tertiary medical centers137 families
- Participants
- 317 patients
- Exposure
- RET C634R vs other C634 mutations
- C634Rn = 133
- C634F/G/S/W/Yn = 184reference
- Outcome
- Aggressiveness and long-term outcomes of hereditary MTC
- Follow-up
- Median 10.6 years (4.9-16.6 years)
Methodological detailsinternational, multicenter, three tertiary medical centers
- International
- Multicenter
- Three tertiary medical centers
Main finding
As reported in the abstract
C634R vs C634F/G/S/W/YEstimate (CI)P value
C634R
HR for distant metastases 2.545(1.134–5.713)
P = 0.024Multivariable analysis
HR for worse disease-specific survival 6.488(1.364–30.862)
P = 0.019- HR for worse disease-specific survival per increasing age
- 1.082 (CI 1.023-1.144); p = 0.006
- HR for worse disease-specific survival with extrathyroidal extension (ETE)
- 9.695 (CI 2.344-40.105); p = 0.002
Observational data: associations, not effects.
Further findings
| Outcome | C634R | C634F/G/S/W/Y | P value |
|---|---|---|---|
| Age at initial surgerySlightly younger with C634R | 27.8 ± 12.1 | 31.3 ± 14.9 | P = 0.025 |
| Primary tumor sizeLarger with C634R | 1.9 ± 1.2 | 1.5 ± 1.1 | P = 0.006 |
- Lymph node metastases (Kaplan-Meier) · higher cumulative rates and earlier occurrence with C634R
- P = 0.0003
- Extrathyroidal extension (Kaplan-Meier) · higher cumulative rates and earlier occurrence with C634R
- P < 0.0001
Original publication
Do Prognostic Differences Exist Among High-Risk RET Mutations? A Comparison of Outcomes Between the RET C634R and Other C634 Mutations in Hereditary Medullary Thyroid Carcinoma. Thyroid. Published 3 September 2025. doi:10.
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