CQ26. What Is the Usefulness of RET Gene Mutation Analysis for Medullary Carcinoma?



It is very important to differentiate whether a medullary carcinoma is hereditary or sporadic when determining the treatment strategy preoperatively. If hereditary, it is either multiple endocrine neoplasia type 2 (MEN 2) or familial medullary thyroid carcinoma (FMTC), which is inherited as autosomal dominants. MEN 2A manifests medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia, and MEN 2B is associated with submucosal neuroma of the tongue and/or lips, hyperextension of the extremities, marfanoid habitus, intestinal ganglioneuromatosis, and thickened corneal nerves, in addition to medullary thyroid carcinoma and pheochromocytoma. FMTC hereditarily develops only as medullary carcinoma. The utility of mutation analysis of the RET gene, which is the responsible gene for MEN 2 and FMTC, is investigated based on the literature


Total Thyroidectomy Medullary Thyroid Carcinoma Multiple Endocrine Neoplasia Type Medullary Carcinoma Autosomal Dominant 
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  1. 1.
    Eng C, Clayton D, Schuffenecker I et al (1996) The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 276:1575–1579 (RS)PubMedCrossRefGoogle Scholar
  2. 2.
    Machens A, Dralle H (2007) Genotype-phenotype based surgical concept of hereditary medullary thyroid carcinoma. World J Surg 31:957–968 (RS)PubMedCrossRefGoogle Scholar
  3. 3.
    Elisei R, Romei C, Cosci B et al (2007) RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J Clin Endocrinol Metab 92:4725–4729 (PS)PubMedCrossRefGoogle Scholar
  4. 4.
    Brandi ML, Gagel RF, Angeli A et al (2001) Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671 (Others)PubMedCrossRefGoogle Scholar
  5. 5.
    Szinnai G, Meier C, Komminoth P et al (2003) Review of multiple endocrine neoplasia type 2A in children: therapeutic results of early thyroidectomy and prognostic value of codon analysis. Pediatrics 111:e132–139 (SR)PubMedCrossRefGoogle Scholar
  6. 6.
    Machens A, Holzhausen HJ, Thanh PN et al (2003) Malignant progression from C-cell hyperplasia to medullary thyroid carcinoma in 167 carriers of RET germline mutations. Surgery 134:425–431 (RS)PubMedCrossRefGoogle Scholar
  7. 7.
    Niccoli-Sire P, Murat A, Rohmer V et al (2003) When should thyroidectomy be performed in familial medullary thyroid carcinoma gene carriers with non-cysteine RET mutations? Surgery 134:1029–1037 (RS)PubMedCrossRefGoogle Scholar
  8. 8.
    Kloos RT, Eng C, Evans DB et al (2009) Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 19:565–612 (Others)PubMedCrossRefGoogle Scholar
  9. 9.
    Machens A, Niccoli-Sire P, Hoegel J et al (2003) Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med 349:1517–1525 (RS)PubMedCrossRefGoogle Scholar
  10. 10.
    Skinner MA, Moley JA, Dilley WG et al (2005) Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med 353:1105–1113 (PS)PubMedCrossRefGoogle Scholar
  11. 11.
    Frank-Raue K, Buhr H, Dralle H et al (2006) Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype. Eur J Endocrinol 155:229–236 (PS)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  1. 1.Department of SurgeryNoguchi Thyroid Clinic and Hospital FoundationBeppuJapan
  2. 2.Department of Breast and Endocrine SurgeryToranomon HospitalTokyoJapan
  3. 3.Department of Endocrine Surgery and Hygiene & Public Health IITokyo Women’s Medical UniversityTokyoJapan

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