Related Experiment Video
Updated: Jun 4, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Dissection of RET p.M918T-driven progression of hereditary vs. sporadic medullary thyroid cancer
Andreas Machens1, Kerstin Lorenz1, Frank Weber2
1Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097, Halle (Saale), Germany.
Background:
Whether inherited in the context of multiple endocrine neoplasia 2B at germline level or acquired in a lifetime, all RET p.M918T (RET c.2753T>C) mutations should activate the RET tyrosine kinase receptor alike, with similar degrees of medullary thyroid cancer (MTC) progression when disparities in disease onset and multifocal growth are accounted for.
Methods:
This cross-sectional analysis of RET p.M918T-driven progression of hereditary MTC (33 patients) vs. sporadic MTC (36 patients) sought to explore this hypothesis.
Results:
Patients with hereditary disease were significantly younger at thyroidectomy (medians of 10 vs. 57 yrs.) and featured significantly more often multifocal growth (69 vs. 14 %) with more thyroid tumor foci (medians of 2 foci vs. 1 focus) than patients with sporadic disease. Although the former had 3.6-fold smaller primary thyroid tumor diameters (medians of 5 vs. 18 mm) and twice as many neck nodes dissected (medians of 66.5 vs. 32 nodes) than the latter, extrathyroid tumor extension (42 vs. 36 %), node metastasis (64 vs. 77 %), distant metastasis (33 vs. 17 %), and biochemical cure rates (45 vs. 35 %) were fairly comparable, as was the number of dissected node metastases (medians of 7 vs. 8 involved nodes). Sensitivity analyses, with breakdown of patients by tumor multifocality and nodal status, corroborated these findings.
Conclusion:
RET p.M918T-driven progression of MTC is similar in hereditary and sporadic disease, barring earlier development and more frequent multifocal growth of hereditary MTC. This makes a compelling case for referral of patients with RET p.M918T-driven MTCs to specialist surgical centers.
Insights
RET p.M918T mutations drive similar medullary thyroid cancer (MTC) progression in hereditary and sporadic cases. Hereditary MTC presents earlier with multifocal growth, but overall disease progression is comparable, supporting referral to specialized centers.
Area of Science:
- Oncology
- Genetics
- Endocrinology
Background:
- All RET p.M918T mutations, whether inherited (multiple endocrine neoplasia 2B) or acquired, are hypothesized to activate the RET tyrosine kinase receptor similarly.
- This activation is expected to lead to comparable medullary thyroid cancer (MTC) progression when accounting for differences in disease onset and multifocal growth.
Purpose of the Study:
- To test the hypothesis that RET p.M918T-driven MTC progression is similar in hereditary and sporadic forms.
- To compare clinical and pathological features between hereditary and sporadic MTC patients with RET p.M918T mutations.
Main Methods:
- Cross-sectional analysis comparing hereditary MTC (33 patients) and sporadic MTC (36 patients) with RET p.M918T mutations.
- Evaluation of patient age at thyroidectomy, tumor multifocality, tumor size, extent of lymph node dissection, and rates of extrathyroidal extension, nodal metastasis, distant metastasis, and biochemical cure.
Main Results:
- Hereditary MTC patients were significantly younger at thyroidectomy (median 10 vs. 57 years) and had more multifocal growth (69% vs. 14%).
- Despite smaller primary tumors and more nodes dissected in hereditary cases, extrathyroid extension, nodal and distant metastasis rates, and biochemical cure rates were comparable.
- Sensitivity analyses confirmed these findings across different tumor multifocality and nodal status subgroups.
Conclusions:
- RET p.M918T-driven MTC progression is similar in hereditary and sporadic disease, with earlier onset and multifocal growth being characteristic of hereditary forms.
- The comparable disease progression underscores the importance of genetic testing for RET mutations in MTC.
- Referral of all patients with RET p.M918T-driven MTCs to specialist surgical centers is recommended for optimal management.
