1. ¹Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
2. ²Department of Otolaryngology/Head and Neck Surgery (Division of Head and Neck Cancer Research), The Johns Hopkins Medical Institutions, Baltimore, MD, USA
3. ³Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA
4. ⁴Department of Molecular Microbiology and Immunology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

Correspondence: Dr WH Westra, MD, The Weinberg Bldg, Room 2242, 401 N. Broadway, Baltimore, MD 21231, USA. E-mail: wwestra@jhmi.edu

Received 7 June 2004; Revised 25 June 2004; Accepted 28 June 2004; Published online 6 August 2004.

Abstract

Papillary thyroid carcinoma may encompass a mixed group of neoplasms where divergence in clinical behavior may reflect distinct genetic alterations. For example, young patients with papillary thyroid carcinoma have a better prognosis than affected adults, and their carcinomas are much more likely to harbor chromosomal rearrangements involving the RET proto-oncogene. Mutational activation of the BRAF oncogene has recently been identified as the most common genetic alteration in papillary thyroid carcinoma, but little is known about its frequency as a function of patient age. We tested 20 papillary thyroid carcinomas from young patients ranging from 10 to 17 years of age for the thymine (T) adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using a newly developed assay that employs a novel primer extension method (Mutector^® assay). The prevalence of BRAF mutation was compared with a larger group of papillary thyroid carcinomas from previously tested adult patients (>20 years). BRAF mutations were not common in papillary thyroid carcinomas from young patients compared to their counterparts in adults (20 vs 77%; OR=13.3, 95% confidence interval (CI)=3.4–56.5; P<0.0001), but they become increasingly prevalent with advancing patient age (OR as a function of age at 10-year intervals=1.80 CI=1.33–2.44; P<0.001). Unlike papillary thyroid carcinomas that arise in adults, mutational activation of BRAF is not a major genetic alteration in papillary thyroid carcinomas that arise in young patients. The increasing frequency of BRAF mutations as a function of age could help account for the well documented but poorly understood observation that age is a relevant prognostic indicator for patients with papillary thyroid carcinoma.