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

Abstract

Background: Evidence for an increased prevalence of BRAFV600E mutations has been documented in recent decades. The aim of this study was to evaluate the prevalence of both RET/PTC rearrangements and BRAFV600E 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 BRAFV600E mutations increased over the same period, from 28% in group 1 (28of100) to 48.9% in group 2 (73 of 148) and 58.1% in group 3 (89 of 153). A consistent increase in BRAFV600E prevalence was observed in the Sicilian group (P<0.0001). Moreover,astatistically 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 BRAFV600E mutations. In addition, the mean age at diagnosis increased and tumor size decreased over the study period. Copyright © 2012 by The Endocrine Society.