Clinical Utility Of BRAF^V600EMutation Detection In Thyroid FNA Liquid-based Cytology Specimens

Objective:Thyroid cancer,most of which is found to be BRAF^V600E gene mutation,is the most common malignancy in the endocrine system.The patient who is suspected as thyroid cancer is normally advised to do a fine-needle aspiration?FNA?biopsy examination.However,about 20%of FNA specimens are still undetermined.we aimed to examine the BRAF^V600E mutation status of LBC residual materials of indeterminate samples and their corresponding surgical tissue counterparts using a validated Amplification Refractory Mutation System Polymerase Chain Reaction?ARMS-PCR?method to evaluate the feasibility of molecular analysis using LBC residual materials and analyze whether the BRAF^V600E mutation analysis could potentially add information to the indeterminate diagnoses and provide a better understanding of these FNA specimens.Method:This study collected thyroid fine needle aspiration liquid-based cytology specimens from No.l Hospital of Jilin University department of laboratory cell pathology December 2015 to February 2016,the inclusion criteria were:1)by two doctors according to the standard of diagnosis of thyroid FNAC Bethesda as the "uncertainty" specimen.The present study included two types of "atypical epithelial cells,suspicious/considered as PTC"?SPTC?and "atypical atypical atypical lesions"?AUS?.2)there are at least 6 or more clusters of cells in each smear,and each cluster has at least more than 10 follicular cells.3)cases were treated by operation so well as confirmed by pathology after operation.The collected specimens using amplification refractory mutation system?amplification refractory mutation system,scorpions,ARMS?method for detection of BRAF^V600E gene mutation in the BRAF^V600E gene mutation status and tissue pathological diagnosis surgery results were compared to evaluate the sensitivity,specificity,accuracy and consistency.Results:A total of 214 cases of thyroid fine needle aspiration cytology specimens were collected from the Department of Pathology,No.l Hospital of Jilin University,from December 2015 to February 2016.Among them,91 cases?42.52%?were diagnosed as"indeterminate".The were 59 cases,of which SPTC was found in 52 cases and AUS in 7 cases.In addition,we selected the remaining samples of PTC liquid based cytology in accordance with the inclusion criteria to detect the mutation of BRAF^V600E gene in.All cases were examined for BRAF^V600E gene mutation.In the surgical treatment of uncertainty for 48 cases of patients,including 44 cases of SPTC(39 cases,4 cases were positive for BRAF^V600E?AUS?2 cases were positive for BRAF^V600E),through telephone follow-up informed of 11 cases?8SPTC,3AUS?were treated in our hospital,including 9 cases?1 cases in 8 cases SPTC,AUS?BRAF^V600E positive,2 cases of AUS negative for BRAF^V600E.After pathological examination,59 cases of FNAC "uncertainty" in the diagnosis of in patients with PTC,in which 3 cases were diagnosed as nodular goiter,in which the diagnosis of medullary thyroid carcinoma in 1 cases.In addition,12 patients with PTC were diagnosed by PTC.55 cases of PTC patients with liquid based cytology positive for the BRAF^V600E gene mutation in 50 cases?90.91%?,including 47 cases of SPTC,3 cases were AUS;3 cases of patients with ng?1 SPTC,2AUS?and in patients with medullary thyroid carcinoma?AUS?of liquid based cytology specimens corresponding to the BRAF^V600E gene mutation negative.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of BRAF^V600E gene mutation were 92.42%,100%,92.86%,44.44%,respectively.And histopathological analysis compared BRAF ARMS-PCR kappa value was 0.582.There is no significant difference between clinical and pathological features of papillary thyroid carcinoma?invasion,lymph node metastasis,multifocal and tumor size?with the results of BRAF^V600E mutation.Conclusion:1)These results indicated that the BRAF^V600E mutation detection in thyroid FNA liqued-based cytology specimens by ARMS-PCR has hight accuracy and operability.2)Detection of BRAF^V600E gene mutations in liquid based cytology specimens can be used as an adjunct test to preoperative diagnosis of PTC.