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Updated: Feb 16, 2026
Employing Digital Droplet PCR to Detect BRAF V600E Mutations in Formalin-fixed Paraffin-embedded Reference Standard Cell Lines
Published on: October 8, 2015
Patient Age-Associated Mortality Risk Is Differentiated by BRAF V600E Status in Papillary Thyroid Cancer
Xiaopei Shen1, Guangwu Zhu1, Rengyun Liu1
1Xiaopei Shen, Guangwu Zhu, Rengyun Liu, and Mingzhao Xing, Johns Hopkins University School of Medicine, Baltimore, MD; David Viola and Rossella Elisei, University of Pisa, Pisa; Efisio Puxeddu, University of Perugia, Perugia; Laura Fugazzola and Carla Colombo, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Auxologico Italiano and University of Milan, Milan; Caterina Mian, University of Padua; Federica Vianello, Veneto Institute of Oncology, IRCCS, Padua, Italy; Barbara Jarzab and Agnieszka Czarniecka, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; Alfred K. Lam, Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland; Christine J. O'Neill, Mark S. Sywak, and Roderick Clifton-Bligh, The University of Sydney, Sydney, New South Wales, Australia; Linwah Yip, University of Pittsburgh School of Medicine, Pittsburgh, PA; Garcilaso Riesco-Eizaguirre, Hospital Universitario La Paz and Hospital Universitario de Móstoles; Garcilaso Riesco-Eizaguirre and Pilar Santisteban, Biomedical Research Institute "Alberto Sols," Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid; Garcilaso Riesco-Eizaguirre and Pilar Santisteban, Ciberonc, Health Institute Carlos III, Madrid, Spain; and Bela Bendlova and Vlasta Sýkorová, Institute of Endocrinology, Prague, Czech Republic.
Abstract:
Purpose For the past 65 years, patient age at diagnosis has been widely used as a major mortality risk factor in the risk stratification of papillary thyroid cancer (PTC), but whether this is generally applicable, particularly in patients with different BRAF genetic backgrounds, is unclear. The current study was designed to test whether patient age at diagnosis is a major mortality risk factor. Patients and Methods We conducted a comparative study of the relationship between patient age at diagnosis and PTC-specific mortality with respect to BRAF status in 2,638 patients (623 men and 2,015 women) with a median age of 46 years (interquartile range, 35 to 58 years) at diagnosis and a median follow-up time of 58 months (interquartile range, 26 to 107 months). Eleven medical centers from six countries participated in this study. Results There was a linear association between patient age and mortality in patients with BRAF V600E mutation, but not in patients with wild-type BRAF, in whom the mortality rate remained low and flat with increasing age. Kaplan-Meier survival curves rapidly declined with increasing age in patients with BRAF V600E mutation but did not decline in patients with wild-type BRAF, even beyond age 75 years. The association between mortality and age in patients with BRAF V600E was independent of clinicopathologic risk factors. Similar results were observed when only patients with the conventional variant of PTC were analyzed. Conclusion The long-observed age-associated mortality risk in PTC is dependent on BRAF status; age is a strong, continuous, and independent mortality risk factor in patients with BRAF V600E mutation but not in patients with wild-type BRAF. These results question the conventional general use of patient age as a high-risk factor in PTC and call for differentiation between patients with BRAF V600E and wild-type BRAF when applying age to risk stratification and management of PTC.
