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.

Although small papillary thyroid cancer (PTC) patients are considered as low-risk population, approximately 5-20% of these patients relapse after surgery. The objective of this single-center retrospective study was to identify risk factors, which could help to distinguish patients who would need additional treatment after surgery. A total of 268 patients (39 men, 229 women, median age 49 years) underwent surgery between 2007absence of metastatic lymph nodes (LN) in the lateral neck compartment (LC), and absence of local invasion. Total thyroidectomy was performed in 252 cases, in 221 cases with central neck compartment (CC) dissection. The outcome-a more aggressive disease-was defined as the presence of metastases in the LNLC or in distant organs found during follow-up. A median followup was 117 months. Overall, 41 patients experienced the outcome with a median time-to-event of 18 months. Male gender (OR = 2.2, P = 0.049), extra-thyroidal extension ETE (OR = 2.61, P = 0.015), and metastases in LNCC (OR = 4.21, P < 0.001) were associated with worse outcome. Multivariable analysis and stratification according to ETE revealed an effect modification with a higher effect of the positive LNCC on the outcome among patients without ETE than in those with ETE. Our findings advocate placing greater emphasis on the role of LNCC metastases in the absence of ETE. In clinically node-negative tumors intraoperative examination of CC on the side of the tumor followed by CC dissection if metastatic lymphadenopathy is present could play an important role in the stratification of patients with small-size PTC.