Modifications in the papillary thyroid cancer gene profile over the last 15 years

J Clin Endocrinol Metab. 2012 Sep;97(9):E1758-65. doi: 10.1210/jc.2012-1269. Epub 2012 Jun 28.

Abstract

Background: Evidence for an increased prevalence of BRAF(V600E) mutations has been documented in recent decades. The aim of this study was to evaluate the prevalence of both RET/PTC rearrangements and BRAF(V600E) mutations in an Italian cohort of papillary thyroid carcinoma (PTC) patients followed at the Endocrine Units of Pisa, Milano, and Perugia from 1996-2010.

Patients and methods: In total, 401 PTC patients were examined and grouped according to the time of surgery: group 1, 1996-2000; group 2, 2001-2005; and group 3, 2006-2010. Patients were analyzed for clinical, pathological, and molecular features. In parallel, the molecular characteristics of 459 PTC from Sicily were studied.

Results: The genetic profiles of the three groups were significantly different (P < 0.0001). In particular, the frequency of RET/PTC rearrangements decreased from 1996-2010, occurring in 33 of 100 (33%) of the patients in group 1, 26 of 148 (17%) in group 2, and 15 of 153 (9.8%) in group 3. The incidence of BRAF(V600E) mutations increased over the same period, from 28% in group 1 (28 of 100) to 48.9% in group 2 (73 of 148) and 58.1% in group 3 (89 of 153). A consistent increase in BRAF(V600E) prevalence was observed in the Sicilian group (P < 0.0001). Moreover, a statistically significant increase in the mean age at diagnosis and decrease in tumor size over the study period was observed.

Conclusion: The genetic profile of PTC changed over the last 15 yr, with a significant decrease in the prevalence of RET/PTC rearrangements and an increase in BRAF(V600E) mutations. In addition, the mean age at diagnosis increased and tumor size decreased over the study period.

Publication types

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

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Carcinoma, Papillary / epidemiology
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Cohort Studies
  • DNA Fingerprinting
  • DNA, Neoplasm / genetics
  • Female
  • Gene Rearrangement
  • Genetic Variation
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-ret / genetics
  • Sicily / epidemiology
  • Thyroid Neoplasms / epidemiology
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology

Substances

  • DNA, Neoplasm
  • Proto-Oncogene Proteins c-ret
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf