Advertisement

Annals of Surgical Oncology

, Volume 18, Issue 1, pp 219–225 | Cite as

Medullary Thyroid Carcinoma: Long-Term Outcomes of Surgical Treatment

  • Deepak T. Abraham
  • Tsu-Hui Low
  • Marinella Messina
  • Nicole Jackson
  • Anthony Gill
  • Angela S. Chou
  • Leigh Delbridge
  • Diana Learoyd
  • Bruce G. Robinson
  • Stan Sidhu
  • Mark Sywak
Endocrine Tumors

Abstract

Background

Medullary thyroid carcinoma (MTC) accounts for 5 to 10% of all thyroid cancers but is responsible for a disproportionate number of deaths.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Medullary Thyroid Carcinoma Central Neck Serum Calcitonin Sporadic Medullary Thyroid Carcinoma Serum Calcitonin Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

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.

References

  1. 1.
    Hazard JB, Hawk WA, Crile G Jr. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. J Clin Endocrinol Metab. 1959;19:152–61.CrossRefPubMedGoogle Scholar
  2. 2.
    Clayman GL, el-Baradie TS. Medullary thyroid cancer. Otolaryngol Clin North Am. 2003;36:91–105.CrossRefPubMedGoogle Scholar
  3. 3.
    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.CrossRefPubMedGoogle Scholar
  4. 4.
    Leboulleux S, Baudin E, Travagli JP, Schlumberger M. Medullary thyroid carcinoma. Clin Endocrinol (Oxf). 2004;61:299–310.CrossRefGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    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.CrossRefPubMedGoogle Scholar
  7. 7.
    Machens A, Dralle H. Genotype-phenotype based surgical concept of hereditary medullary thyroid carcinoma. World J Surg. 2007;31:957–68.CrossRefPubMedGoogle Scholar
  8. 8.
    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.CrossRefPubMedGoogle Scholar
  9. 9.
    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.CrossRefGoogle Scholar
  10. 10.
    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.CrossRefPubMedGoogle Scholar
  11. 11.
    Boikos SA, Stratakis CA. Molecular mechanisms of medullary thyroid carcinoma: current approaches in diagnosis and treatment. Histol Histopathol. 2008;23:109–16.PubMedGoogle Scholar
  12. 12.
    Kloos RT, Eng C, Evans DB, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19:565–612.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    Raue F, Frank-Raue K. Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. Hormones (Athens). 2009;8:23–8.Google Scholar
  15. 15.
    Skinner MA, Moley JA, Dilley WG, et al. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. 2005;353:1105–13.CrossRefPubMedGoogle Scholar
  16. 16.
    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.CrossRefGoogle Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    Pillarisetty VG, Katz SC, Ghossein RA, Tuttle RM, Shaha AR. Micromedullary thyroid cancer: how micro is truly micro? Ann Surg Oncol (in press).Google Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    Mathew CG, Smith BA, Thorpe K, et al. Deletion of genes on chromosome 1 in endocrine neoplasia. Nature. 1987;328(6130):524–6.CrossRefPubMedGoogle Scholar
  21. 21.
    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.Google Scholar

Copyright information

© Society of Surgical Oncology 2010

Authors and Affiliations

  • Deepak T. Abraham
    • 1
    • 2
  • Tsu-Hui Low
    • 1
  • Marinella Messina
    • 2
  • Nicole Jackson
    • 2
  • Anthony Gill
    • 3
  • Angela S. Chou
    • 3
  • Leigh Delbridge
    • 1
  • Diana Learoyd
    • 4
  • Bruce G. Robinson
    • 4
  • Stan Sidhu
    • 1
    • 2
  • Mark Sywak
    • 1
  1. 1.Department of Surgery, University Clinic, Royal North Shore HospitalUniversity of Sydney Endocrine Surgical UnitSt Leonards, SydneyAustralia
  2. 2.Cancer Genetics Unit, Kolling Institute of Medical ResearchUniversity of SydneySydneyAustralia
  3. 3.Department of Anatomical Pathology, Royal North Shore HospitalUniversity of SydneySydneyAustralia
  4. 4.Department of Endocrinology, Royal North Shore HospitalUniversity of SydneySydneyAustralia

Personalised recommendations