Medullary thyroid carcinoma (MTC) accounts for 5 to 10% of all thyroid cancers but is responsible for a disproportionate number of deaths.
We performed a retrospective review to describe clinical outcomes in patients with medullary thyroid carcinoma, screening a subset of patients for somatic mutations in the RET and p18 genes and performing genotype-phenotype correlation in a tertiary-care referral hospital from 1967 to 2009.
We studied a total of 94 patients identified from a prospectively maintained thyroid cancer database. Data gathered included patient demographics, serum calcitonin, clinical outcomes, histopathology, genetic analysis, and status at final follow-up. A subset cohort (n = 50) was screened for somatic mutations in the RET gene and the three exons of the p18 gene. The subset cohort was composed of hereditary medullary thyroid carcinoma (HMTC) (n = 19, index patients = 10, screen detected = 9) and sporadic medullary thyroid carcinoma (SMTC) (n = 31). There were no mutations in the p18 gene in the subset cohort.
A total of 67 SMTC and 27 (28.7%) HMTC cases identified. SMTC were older at initial presentation (52 vs. 34, P = 0.003), had higher preoperative serum calcitonin levels (7968 vs. 1346 ng/L, P = 0.008), and had lymph node recurrence (P = 0.001) compared to HMTC. The tumors were smaller in HMTC (P = 0.038). Overall 10-year survival in SMTC versus HMTC was 69 versus 93% (P = 0.12). On multivariate analysis, vascular invasion (hazard ratio 6.4, P = 0.019) was an adverse predictor for disease-free survival. HMTC in the era of RET analysis presents with a smaller primary tumor, lower preoperative serum calcitonin levels, and lower rates of lymph node metastasis. Mutations in the p18 gene were not a major factor in medullary thyroid carcinoma tumorigenesis.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Hazard JB, Hawk WA, Crile G Jr. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. J Clin Endocrinol Metab. 1959;19:152–61.
Clayman GL, el-Baradie TS. Medullary thyroid cancer. Otolaryngol Clin North Am. 2003;36:91–105.
Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the US, 1985–1995. Cancer. 1998;83:2638–48.
Leboulleux S, Baudin E, Travagli JP, Schlumberger M. Medullary thyroid carcinoma. Clin Endocrinol (Oxf). 2004;61:299–310.
Mole SE, Mulligan LM, Healey CS, Ponder BA, Tunnacliffe A. Localisation of the gene for multiple endocrine neoplasia type 2A to a 480 kb region in chromosome band 10q11.2. Hum Mol Genet. 1993;2:247–52.
Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;86:5658–71.
Machens A, Dralle H. Genotype-phenotype based surgical concept of hereditary medullary thyroid carcinoma. World J Surg. 2007;31:957–68.
Mulligan LM, Marsh DJ, Robinson BG, et al. Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium. J Intern Med. 1995;238:343–6.
van Veelan W, Klompmaker R, Gloerich M, et al. P18 is a tumor suppressor gene involved in human medullary thyroid carcinoma and pheochromocytoma development. Int J Cancer. 2009;124:339–45.
Marsh DJ, Theodosopoulos G, Howell V, et al. Rapid mutation scanning of genes associated with familial cancer syndromes using denaturing high-performance liquid chromatography. Neoplasia. 2001;3:236–44.
Boikos SA, Stratakis CA. Molecular mechanisms of medullary thyroid carcinoma: current approaches in diagnosis and treatment. Histol Histopathol. 2008;23:109–16.
Kloos RT, Eng C, Evans DB, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19:565–612.
Machens A, Holzhausen HJ, Thanh PN, Dralle H. Malignant progression from C-cell hyperplasia to medullary thyroid carcinoma in 167 carriers of RET germline mutations. Surgery. 2003;134:425–31.
Raue F, Frank-Raue K. Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. Hormones (Athens). 2009;8:23–8.
Skinner MA, Moley JA, Dilley WG, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. 2005;353:1105–13.
Learoyd DL, Gosnell J, Elston MS, et al. Experience of prophylactic thyroidectomy in multiple endocrine neoplasia type 2A kindreds with RET codon 804 mutations. Clin Endocrinol (Oxf). 2005;63:636–41.
Moley JF, DeBenedetti MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg. 1999;229:880–7.
Pillarisetty VG, Katz SC, Ghossein RA, Tuttle RM, Shaha AR. Micromedullary thyroid cancer: how micro is truly micro? Ann Surg Oncol (in press).
Marsh DJ, Theodosopoulos G, Martin-Schulte K, et al. Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab. 2003;88:1866–72.
Mathew CG, Smith BA, Thorpe K, et al. Deletion of genes on chromosome 1 in endocrine neoplasia. Nature. 1987;328(6130):524–6.
van VW, van Gasteren CJ, Acton DS, et al. Synergistic effect of oncogenic RET and loss of p18 on medullary thyroid carcinoma development. Cancer Res. 2008;68:1329–37.
D.T.A. is a recipient of the Endeavour International Postgraduate Research Scholarship. S.S. is a NSW Cancer Institute Fellow.
Conflict of interest
The authors declare no conflict of interest.
M. Sywak and S. Sidhu contributed equally to this work.
About this article
Cite this article
Abraham, D.T., Low, T., Messina, M. et al. Medullary Thyroid Carcinoma: Long-Term Outcomes of Surgical Treatment. Ann Surg Oncol 18, 219–225 (2011). https://doi.org/10.1245/s10434-010-1339-y
- Medullary Thyroid Carcinoma
- Central Neck
- Serum Calcitonin
- Sporadic Medullary Thyroid Carcinoma
- Serum Calcitonin Level