中文摘要：

目的：探讨术前超声引导下细针抽吸细胞学检查（US-FNAB）联合BRAF^T1799A突变、RET/PTC1及RET/PTC3重排对诊断甲状腺乳头状癌（PTC）的特异性及敏感性,为临床术前准确诊断PTC选择适用的分子标记物。方法：收集346个超声怀疑为甲状腺恶性结节的US-FNAB细胞标本及对应结节（152个）的术后新鲜组织,采用PCR分别扩增BRAF^T1799A、RET/PTC1及RET/PTC3基因,产物经基因测序证实。结果：346个甲状腺术前穿刺的结节中,选择观察而未手术的结节192个,手术治疗152个,未接受手术建议的结节2个。术前US-FNAB的细胞标本中共检测到51个结节发生BRAF^T1799A突变,其细胞学分类为36个恶性,11个可疑恶性,4个良性。该51个结节术后病理证实均为PTC。20个发生RET/PTC1重排,其术前细胞学结果为17个恶性,2个可疑恶性,1个滤泡性肿瘤或可疑滤泡性肿瘤,术后病理证实均为PTC。3个结节发生RET/PTC3重排,其术前细胞学结果为恶性,术后病理证实均为PTC。对45个术前US-FNAB标本检测BRAF^T1799A突变阴性而术后病理证实为PTC的结节,将其对应结节的术中组织行该基因的检测,仅有1个结节的术后组织中检测到该突变。本研究中,术前US-FNAB联合多分子标志物的检测,将细胞学诊断PTC的敏感度由73.96%提高到92.71%。结论：术前US-FNAB联合多分子标志物的检测可提高其诊断PTC的敏感性及特异性,并有助于患者的个体化诊治。

英文摘要：

Objective： To study the sensitivity and specificity of US-FNAB＇s （Ultrasound-fine needle aspiration biopsy, US-FNAB） combined with the analysis of BRAF^T1799A, RET/PTC rearrangements in preoperative diagnosis of papillary thyroid carcinoma （PTC） diagnosis in order to provide useful molecular biomarkers for preoperative precise diagnosis of PTC. Methods： Thyroid US-FNAB specimens from 346 nodules with suspicious malignancy risk of US features and 152 corresponding surgical samples were examined for the presence of BRAF^T1799A, RET/PTC rearrangements by PCR. DNA sequencing and analysis were performed. Results： Of the 346 nodules, 192 nodules were clinically observed, 152 nodules underwent surgery, and 2 nodules refused suggestions of surgery. 51 BRAF^T1799A mutations were found in FNAB specimens, of which 36 nodules were cytologically diagnosed carcinoma and 11 were indeterminate and 4 were benign. 20 RET/PTC1 rearrangements were found in FNAB specimens, of which 17 nodules were cytologically diagnosed carcinoma and 2 were indeterminate and 1 follicular adenomas. 3 RET/PTC3 rearrangements were found in FNAB specimens which were cytologically diagnosed carcinoma. All nodules with the above molecular biomarkers were confirmed PTC after thyroidectomy. BRAF^T1799A mutation analysis was performed on the surgical specimens from the 45 histologically diagnosed PTC that were negative in US-FNAB samplings. Only one case was negative. Molecular biomarkers analysis significantly enhanced the diagnostic value of cytology for PTC from 73.96 % to 92.71%. Conclusions： Molecular biomarkers analysis can significantly enhance the diagnostic value of cytology for PTC and is also helpful for personal diagnosis and treatment.