The Value Of BRAF^V600E Gene Mutation Combined With High Frequency Ultrasound In Diagnosis Of Thyroid Nodule

BackgroundThyroid nodule is a common clinical disease.In recent years,the incidence rate has increased significantly.The detection rate of high frequency ultrasound in the random population is 19%⁶7%,of which thyroid cancer accounts for about5%¹5%.Papillary thyroid carcinoma accounts for the highest proportion of thyroid cancer,accounting for 60%of adult thyroid cancer and the total number of thyroid cancers in children.In recent years,with the in-depth study of the pathogenesis of thyroid cancer,it is found that the occurrence and development of thyroid cancer are mainly gene mutation and gene rearrangement,the mutation of BRAF^V600E gene is the most common mutation gene in thyroid cancer,especially in papillary thyroid carcinoma.The mutation rate of BRAF^V600E600E gene in papillary thyroid carcinoma can reach27%⁹0%,and the mutation is highly specific.Many studies have shown that BRAF^V600E gene mutation is also closely related to the clinicopathological features and biological behavior of papillary thyroid carcinoma,For example,the mutation rate of the BRAF^V600E gene in the classic papillary thyroid carcinoma is higher than that of the follicular variant.The mutation of the BRAF^V600E gene is more likely to occur in the extrathyroidal extension and lymph node metastasis.Therefore,the analysis of the mutation of the BRAF^V600E gene can help to judge the prognosis of the papillary thyroid carcinoma.High frequency ultrasound,with its high accuracy,easy operation and economic advantages,has become the most commonly used imaging method for the diagnosis of thyroid nodules,but it is not reliable to evaluate malignant nodules by single ultrasound feature.TI-RADS classification is a comprehensive evaluation of multiple ultrasonic signs,and can be used for risk stratification of thyroid nodules,In the process of clinical diagnosis of thyroid nodules,BRAF^V600E gene mutation detection combined with TI-RADS classification can effectively improve the diagnostic accuracy of thyroid cancer,at the same time,To analyze the clinicopathological features and ultrasonic signs associated with BRAF^V600E gene mutation in papillary thyroid carcinoma can provide more evidence for the diagnosis and treatment of thyroid tumors and prognosis.Part 1 Diagnostic efficiency of BRAF^V600E gene mutation detection combined with ACR TI-RADS classification in thyroid nodulesObjective:To compare the value of ACR Thyroid Imaging Reporting and Data System（ACR TI-RADS）,BRAF^V600E gene mutation detection combined with ACR TI-RADS classification in the differential diagnosis of benign and malignant thyroid nodules.Methods:A total of 307 patients with suspicious malignant thyroid nodules diagnosed by high-frequency ultrasonography in our hospital from November 2016 to December 2017 were enrolled in the study.And all patients underwent fine needle aspiration biopsy and BRAF^V600E gene mutation detection.The position,number,size,shape,margin,composition,echogenicityl and echogenic foci of thyroid nodules were recorded by high frequency ultrasound examination.All the ultrasonic image datas were evaluated by 2 senior ultrasound physicians according to 2017 ACR TI-RADS without providing pathological results.The detection of BRAF^V600E gene was divided into mutation type（amplification signal）and wild type（no amplification signal）according to the test results.Taking the pathological results as the gold standard,The diagnostic efficiency of TI-RADS,BRAF^V600E gene mutation detection combined with TI-RADS classification was evaluated by constructing receiver operating characteristic,and the sensitivity,specificity,accuracy,positive predictive value and negative predictive value were compared,and were statistically different（P<0.05）.Results:The malignant rates of TI-RADS 3,4 and 5 categories were 6.25%,31.94%and 84.24%respectively.The area under ROC curve of TI-RADS classification and BRAF^V600E gene mutation detection combined with TI-RADS classification for thyroid nodules was 0.792（95%confidence interval:0.742⁰.836）and 0.835（95%confidence interval:0.789⁰.875）.The two difference was statistically significant（Z=4.046,P=0.000）,The best cut-off point of TI-RADS classification was TI-RADS 5.In the diagnosis of thyroid nodule,the sensitivity,specificity,accuracy,positive predictive value and negative predictive value of TI-RADS classification were 87.24%,71.17%,81.43%,84.24%,75.96%,respectively,The BRAF^V600E gene mutation detection combined with TI-RADS classification were94.89%,71.17%,86.32%,85.32%,88.76%.Conclusions:In practical application,the malignant risk of ACR TI-RADS 4and 5 is higher than the recommended range of guidelines and should be paid attention to in clinical application.ACR TI-RADS classification,BRAF^V600E gene mutation detection combined with ACR TI-RADS classification all have certain diagnostic value for thyroid nodules.The diagnostic efficiency of BRAF^V600E gene mutation detection combined with the ACR TI-RADS classification is better than that of the simple ACR TI-RADS classification.In clinical practices,the malignant possible nodules are considered in the ACR TI-RADS classification,and the detection of BRAF^V600E gene can improve the accuracy of preoperative diagnosis.Part 2 The correlation analysis of BRAF^V600E600E gene mutation in papillary thyroid carcinoma with clinicopathological features and ultrasound featuresObjective:To investigate the correlation of BRAF^V600E gene mutation in papillary thyroid carcinoma with clinicopathological features and ultrasound features.Methods:A total of 175 cases of papillary thyroid carcinoma were treated with thyroid surgery in our hospital from January 2017 to December 2017 were enrolled in the study.The high frequency ultrasound examination was performed in our hospital before the operation,and the BRAF^V600E gene mutation was detected in the postoperative pathological specimens.The detection of BRAF^V600E gene was divided into mutation type（amplification signal）and wild type（no amplification signal）according to the test results.Univariate analysis was used to compare the differences in clinicopathological features（including sex,age,size,number,extrathyroidal extension,metastatic cervical lymph nodes,TNM staging）,and ultrasoound features（including shape,composition,margin,echogenicityl and echogenic foci）between the two groups.The features that showed difference according to the univariate analysis were then processed by multiple binary logistic regression to screen the clinicopathologic features and ultrasound features correlated to BRAF^V600E gene mutation.Results:The univariate analysis showed that the clinicopathological features associated with the BRAF^V600E gene mutation in papillary thyroid carcinoma were:sex,extrathyroidal extension,metastatic cervical lymph nodes and TNM staging,and ultrasound features were:margin and echogenicityl.Multiple binary logistic regression analysis showed that extrathyroidal extension,metastatic cervical lymph nodes and margin were significantly related to BRAF^V600E gene mutation.Conclusions:The mutation of BRAF^V600E gene in papillary thyroid carcinoma is correlated with the clinicopathological features and the ultrasonographic features.Patients with extrathyroidal extension,metastatic cervical lymph nodes and patients with irregular nodule margin displayed by high-frequency ultrasound scanning are more likely to be correlated to BRAF^V600E gene mutations.Preoperative high frequency ultrasound can predict the mutation of BRAF^V600E gene to some extent,and may also be one of the related factors in judging the prognosis of papillary thyroid carcinoma.It provides a basis for clinical diagnosis and treatment,but more sample studies are needed to confirm it.