title: Early malignant progression of hereditary medullary thyroid cancer.
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.
authors.affiliation: Klinik für Allgemein-, Viszeral-, und Gefässchirurgie, Martin-Luther-Universität Halle-Wittenberg, Halle, Saale, Germany. gensurg@medzin.uni-halle.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Machens
authors.forename: Patricia
authors.initials: P
authors.lastname: Niccoli-Sire
authors.forename: Josef
authors.initials: J
authors.lastname: Hoegel
authors.forename: Karin
authors.initials: K
authors.lastname: Frank-Raue
authors.forename: Theo J
authors.initials: TJ
authors.lastname: van Vroonhoven
authors.forename: Hans-Dietrich
authors.initials: HD
authors.lastname: Roeher
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wahl
authors.forename: Peter
authors.initials: P
authors.lastname: Lamesch
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Raue
authors.forename: Bernard
authors.initials: B
authors.lastname: Conte-Devolx
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
mesh_terms: D000293:Adolescent; D000367:Age Factors; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D002648:Child; D003062:Codon / Q000235:genetics; D018450:Disease Progression; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D006965:Hyperplasia; D008197:Lymph Node Excision; D008297:Male; D009367:Neoplasm Staging; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012306:Risk; D011795:Surveys and Questionnaires; D013961:Thyroid Gland / Q000473:pathology / Q000601:surgery; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D013965:Thyroidectomy
chemical_list: D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases