Braf Mutation And Clinical Feature Research In Papillary Thyroid Carcinoma

Background:Although the prognosis of patients with papillary thyroid carcinoma, especially papillary thyroid microcarcinoma (PTMC) is well, occult carcinoma is common in the contralateral lobe or lymph nodes in some patients. Recurrence can be observed because of inappropriate resection extent in PTMC during the follow-up period. BRAF V600E mutation is a common gene mutation type in papillary thyroid carcinoma.It was reported that fine-needle aspiration (FNA) combined with BRAF V600E mutation testing might improve diagnostic accuracy in papillary thyroid carcinoma.Also BRAF V600E mutation was supposed to be related to poor prognosis of thyroid carcinoma. How to examine predictive factors including BRAF V600E mutation for high risk patients of papillary thyroid carcinoma is a current research hotspot.Objective:I.To investigate occult contralateral carcinoma in patients with unilateral PTMC and occult central lymph node metastasis in PTMC patients with clinically node-negative neck(cN0).II.To evaluate the clinical role of BRAF V600E mutation testing in FNA of thyroid nodules.Methods:There are two chapters in this research. Chapter I.The study included89consecutive unilateral PTMC with benign nodules in the contralateral lobe by preoperative image studies or FNA from January2011to December2013. The patients received total thyroidectomies and central lymph node dissections. BRAF V600E mutation was tested on postoperative paraffin specimens.The frequency and predictive factors for occult contralateral carcinoma and occult central lymph node metastasis in these patients were analyzed. Chapter II.The study included83nodules who underwent FNA from March2013to September2013. Cytological specimens were collected to analyze BRAF V600E mutation.Diagnostic performances of cytology and cytology with BRAF V600E mutation analysis were compared according to postoperative pathological diagnosis.Meanwhile,the ralation of BRAF V600E mutation with clinical factors were analyzed. Results:Chapter I. A total of36patients (40.4%) had occult PTMC in the contralateral lobe and the maximum diameter of occult contralateral papillary carcinoma was0.33±0.21cm.Of the79patients with cNO PTMC,31(39.2%) had occult central lymph node metastasis.The number of metastasis lymph nodes was2.71±2.10. On univariate analysis, occult carcinoma in the contralateral lobe or central lymph node metastasis was not associated with patient age,sex,family history,tumor size,Hashimoto’s thyroiditis, extrathyroidal extension,multifocality and BRAF V600E mutation.Chapter Ⅱ.Of83nodules,48nodules were confirmed pathologically postoperatively.BRAF V600E mutation was found in25samples with histologic confirmation of thyroid carcinoma after thyroidectomy,13of which were cytologically diagnosed as carcinoma.16noudles were histologic confirmation of thyroid carcinoma after thyroidectomy among the23BRAF V600E negative noudles,5of which were cytologically diagnosed as carcinoma. Biomolecular analysis significantly increased cytology sensitivity for papillary thyroid carcinoma from43.9%to73.2%(P<0.05). On univariate analysis,the BRAF V600E mutation was associated with extrathyroidal extension(x2=5.227,P=0.022),but patient sex,age,tumor size,lymph node metastasis, multifocality and AJCC stage were not significantly associated with the BRAF V600E mutation.Conclusions:The phenomenon of occult carcinoma is common in patients with unilateral PTMC accompanied with "benign" nodules in the contralateral lobe.From the current data,it is diffcult to distinguish these patients and needs further research.BRAF V600E mutation analysis can significantly improve FNA diagnostic accuracy and maybe useful for prediction of high-risk of thyroid carcinoma.