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Previous Volume 349:1517-1525 October 16, 2003 Number 16 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Cote, G. J. Letters Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background An age-related progression from C-cell hyperplasia to medullary thyroid carcinoma is associated with various germ-line mutations in the rearranged during transfection (RET) proto-oncogene that could be used to identify the optimal time for prophylactic surgery.

Methods In this European multicenter study conducted from July 1993 to February 2001, we enrolled patients who had a RET point mutation in the germ line, were 20 years of age or younger, were asymptomatic, and had undergone total thyroidectomy after confirmation of the RET mutation. Exclusion criteria were medullary thyroid carcinomas of more than 10 mm in greatest dimension and distant metastasis.

Results Altogether, 207 patients from 145 families were identified. There was a significant age-related progression from C-cell hyperplasia to medullary thyroid carcinoma and, ultimately, nodal metastasis in patients whose RET mutations were grouped according to the extracellular- and intracellular-domain codons affected and in those with the codon 634 genotype. No lymph-node metastases were noted in patients younger than 14 years of age. The age-related penetrance was unaffected by the type of amino acid substitution encoded by the various codon 634 mutations. The codon-specific differences in the age at presentation of cancer and the familial rates of concomitant adrenal and parathyroid involvement suggest that the risk of progression was based on the transforming potential of the individual RET mutation.

Conclusions These data provide initial guidelines for the timing of prophylactic thyroidectomy in asymptomatic carriers of RET gene mutations.

Source Information

From the Klinik für Allgemein-, Viszeral-, und Gefäßchirurgie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany (A.M., H.D.); the Centre Hospitalier Régional et Universitaire de Marseille, Service d'Endocrinologie et Maladies Métaboliques, Marseilles, France (P.N.-S., B.C.-D.); the Abteilung Biometrie und Medizinische Dokumentation, Universität Ulm, Ulm, Germany (J.H.); the Endokrinologische Gemeinschaftspraxis, Heidelberg, Germany (K.F.-R., F.R.); the Department of Surgery, University Hospital Utrecht, Utrecht, the Netherlands (T.J.V.); the Klinik für Allgemeine und Unfallchirurgie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany (H.-D.R.); the Chirurgische Klinik, Bürgerhospital Frankfurt am Main, Frankfurt am Main, Germany (R.A.W.); and the Chirurgische Klinik und Poliklinik für Abdominal-, Transplantations-, und Gefäßchirurgie, Universität Leipzig, Leipzig, Germany (P.L.).

Address reprint requests to Dr. Machens at the Klinik für Allgemein-, Viszeral-, und Gefäßchirurgie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Straße 40, D-06097 Halle (Saale), Germany, or at gensurg{at}medzin.uni-halle.de.

Full Text of this Article

Related Letters:

Early Malignant Progression of Hereditary Medullary Thyroid Cancer
Machens A.
Extract | Full Text | PDF  
N Engl J Med 2004; 350:943, Feb 26, 2004. Correspondence

Childhood Progression of Hereditary Medullary Thyroid Cancer
Chabre O., Piolat C., Dyon J.-F., Machens A., Hoegel J., Dralle H.
Extract | Full Text | PDF  
N Engl J Med 2007; 356:1583-1585, Apr 12, 2007. Correspondence

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