Association Of The BRAF^V600E Mutation And Preoperative Inflammatory Markers With Central Lymph Node Metastases In Patients With CN0 Papillary Thyroid Microcarcinoma

Objective:Papillary thyroid microcarcinoma(PTMC)is a common pathological type of thyroid cancer,and the incidence of PTMC has been increasing over the past decades.Although most patients with PTMC have excellent prognosis,central lymph node metastasis(CLNM)are found in many patients,and is associated with an increased risk of local recurrence and mortality.In recent years,BRAFV600E mutation and preoperative inflammatory markers have been found to be significantly correlated with CLNM.The purpose of our study is to verify the predictive role of BRAFV600E mutation and preoperative inflammatory markers,and investigate the interactive effect of BRAFV600E mutation and provides reference for more precise and scientific treatment of PTMC patients.Methods:A total of 442 cNO PTMC patients who under went thyroid ectomy with pCLND in the department of thyroid surgery at the Second Hospital of Hebei Medical University were analyzed.The relations of CLNM with clinicopathologic characteristics(age,sex,tumor size,multifocality,bilateralism,capsular invasion and central lymph node metastasis)of cNO PTMC were analyzed by univariate and multivariate analysis.The BRAFV600E mutation was confirmed by the Ventana IHC method.Neutrophil-to-lymphocyte ratio(NLR)and Platelet-lymphocyte ratio(PLR)were calculated from the full blood count routinely performed before surgery.Single factor adopted ?2 test and multivariate logistic regression analysis revealed the independent risk factor with CLNM.The interactive effect of BRAFV600E mutation and inflammatory markers on CLNM was evaluated through relative excess risk of interaction(RERI),attributable proportion(AP),and synergy index(SI).Results:1.There were 184(41.6%)with CLNM,263(59.5%)with BRAFV600E mutation,191(43.2%)with NLR>2.5,199(45.0%)with PLR>175 of 442 cNO PTMC patients.BRAFV600E mutation,NLR?2.5,PLR?175 central lymph node metastasis were 133(72.3%),116(63.0%)and 94(51.1%).Multivariate logistic regression analysis revealed that tumor size?5mm,multifocality,capsular invasion,BRAFV600E mutation,NLR>2.5,PLR?175 were independent risk factors of CLNM in patients with cNO PTMC(P<0.05).2.Patients with BRAFV600E mutation and NLR<2.5 or patients without BRAFV600E mutation and NLR>2.5 had higher risk of CLNM than patients without BRAFV600E mutationand NLR<2.5(P<0.05).Patients with BRAFV600E mutation and NLR>2.5 had the highest risk of CLNM(P<0.05).The interactive effect of BRAFV600E mutation and NLR showed:RERI=5.531(0.160-10.901),AP=0.512(0.230-0.794),SI=2.294(1.492-4.579).3.Patients without BRAFV600E mutation and NLR<2.5 were defined as negative,patients with BRAFV600E mutation or NLR>2.5 were defined as positive.Diagnostic analysis showed that the sensitivity was 90%,the specificity was 89%,the Youden index was 79%,the positive predictive value was 86%,and the negative predictive value was 93%.Conclusions:1.Tumor size?5mm,multifocality,capsular invasion,BRAFV600E mutation,NLR>2.5,and PLR>175 were independent risk factors of CLNM in patients with cNO PTMC.2.BRAFV600E mutation and NLR>2.5 were the most important independent risk factors of CLNM in patients with PTMC.A significant additive interaction was found between BRAFV600E mutation and NLR,promote central lymph node metastasis.3.BRAFV600E mutation combined with NLR can effectively predict the presence of CLNM in patients with cNO PTMC.