Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey

J Clin Res Pediatr Endocrinol. 2016 Mar 5;8(1):13-20. doi: 10.4274/jcrpe.2219. Epub 2015 Dec 18.

Abstract

Objective: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed.

Methods: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients.

Results: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years.

Conclusion: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family counselling.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Carcinoma, Medullary / congenital*
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / pathology
  • Carcinoma, Medullary / surgery
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Humans
  • Male
  • Multiple Endocrine Neoplasia Type 2a / genetics*
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Multiple Endocrine Neoplasia Type 2a / surgery
  • Mutation / genetics*
  • Prognosis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret / genetics*
  • Retrospective Studies
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / surgery
  • Thyroidectomy
  • Turkey

Substances

  • Biomarkers
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret
  • RET protein, human

Supplementary concepts

  • Familial medullary thyroid carcinoma