RET proto-oncogene mutations affecting codon 790/791: A mild form of multiple endocrine neoplasia type 2A syndrome?

Surgery. 2002 Dec;132(6):952-9; discussion 959. doi: 10.1067/msy.2002.128559.

Abstract

Background: In patients with multiple endocrine neoplasia type 2A syndrome, prophylactic thyroidectomy is generally recommended at the age of 5 to 6 years. Whether this recommendation is justified for exon 13 mutations is unknown.

Methods: We analyzed the clinical data from 40 patients harboring RET codon 790/791 mutations (exon 13) who had been treated in 4 specialized centers.

Results: Mean age was 35.2 +/- 21.6 years (range, 5.1-69.0 years). Thirteen patients were index patients (mean age, 57.7 +/- 11.3 years), 27 patients were screening patients (mean age, 24.4 +/- 16.5 years). In the index group, pT-category was: T0, n = 2; T1, n = 6; T2, n = 2; T3, n = 1; and T4, n = 2. Lymph node metastases were found in 5 patients and distant metastases in 1 patient. Postoperatively, 69% of index patients were biochemically cured. In the screening group, pT-category was: T0, n = 19; T1, n = 7; and T2, n = 1. Lymph node metastases were found in 2 patients. Postoperatively, 93% of screening patients were biochemically cured. The youngest patient with medullary thyroid carcinoma was 13.8 years, the youngest patient with lymph node metastases was 46.4 years.

Conclusions: Patients with RET codon 790/791 mutations seemed to have a less aggressive clinical course compared with patients with classic multiple endocrine neoplasia type 2A syndrome. Still, index patients had a lower biochemic cure rate in comparison with screening patients. Timely total thyroidectomy including lymph node dissection is warranted.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / genetics*
  • Adrenal Gland Neoplasms / pathology
  • Adult
  • Aged
  • Carcinoma, Medullary / genetics*
  • Carcinoma, Medullary / secondary
  • Child
  • Child, Preschool
  • Drosophila Proteins*
  • Female
  • Germ-Line Mutation
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 2a / genetics*
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Pheochromocytoma / genetics*
  • Pheochromocytoma / pathology
  • Point Mutation
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology

Substances

  • Drosophila Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila