A different prognostic value of BRAFV600E mutation positivity in various age groups of patients with papillary thyroid cancer

The aim of the retrospective single-center study was to assess the prognostic value of BRAFV600E mutation positivity (BRAFV600E+) on disease persistence/recurrence in patients with papillary thyroid cancer (PTC). A total of 199 patients having had initial surgery with neck dissection in our hospital between 6/2009-6/2012 were included in the cohort. Excluded were patients with unifocal microcarcinoma ≤1cm. BRAFV600E mutation was tested from formalin-fixed paraffin-embedded surgicaly removed tumors. All included patients were postoperatively treated with radioiodine. The median duration of follow-up was 43 months, quartiles range 30 - 58 months. Variables included in the final model: BRAFV600E+, categorised age, sex, and high-risk status, or alternatively lymph node status. Based on differences in persistence/recurrence rates, patients were divided into three age categories (<35, 35-60, ≥60). Multiple regression analysis showed a significant interaction between BRAFV600E+ and age, modifying the effect of BRAFV600E+ on persistence/recurrence. BRAFV600E+ in low-risk patients of any age and in high-risk middle-aged patients did not confer additional hazard compared with BRAFV600E mutation negative (BRAFV600E-) low-risk and BRAFV600E- high-risk patients, respectively. However, younger (<35 years) and older (≥60 years) high-risk BRAFV600E+ patients had 17.28 and 33.49-fold increased hazard of persistence/recurrence, respectively, compared with low-risk BRAFV600E- patients. The alternative model including lymph node status yielded similar results for the prognostic significance of BRAFV600E+ in younger and older patients. In conclusion, the prognostic value of BRAFV600E+ depends on high-risk status and likely on age-associated factors. Such additional knowledge could change clinical decision-making in treatment modality.