No correlation between RET immunostaining and the codon 918 mutation in sporadic medullary thyroid carcinoma

Langenbecks Arch Surg. 1999 Feb;384(1):60-4. doi: 10.1007/s004230050175.


Introduction: Medullary thyroid carcinoma (MTC) occurs sporadically or as part of the inherited cancer syndrome, multiple endocrine neoplasia (MEN) type 2. The MEN2 gene has been identified as the RET proto-oncogene. Mutations in the RET proto-oncogene are associated with the pathogenesis of MTC. Approximately 23-40% of sporadic MTCs (sMTCs) have a somatic RET codon 918 mutation within the catalytic core of the tyrosine kinase, which is a mutation found in over 98% of all MEN 2B cases as a germline mutation.

Methods: In order to elucidate the role of this mutation, we examined 40 sMTCs for the codon 918 mutation. Simultaneously, we looked for overexpression of the RET protein by means of immunohistochemistry with a newly developed RET antibody.

Results: In 8 of 40 tumors (20%), we were able to find a RET codon 918 mutation. Nine of 40 tumors (22.5%) showed immunoreactivity with the RET antibody.

Conclusion: The presence of the somatic RET codon 918 mutations did not correlate with the presence of positive RET immunostaining.

MeSH terms

  • Carcinoma, Medullary / genetics*
  • Codon / genetics*
  • Humans
  • Immunohistochemistry
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Mutation*
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogenes*
  • Thyroid Neoplasms / genetics*


  • Codon
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases