BRAF V600E突变与甲状腺乳头状癌临床病理特征的相关性

目的:探讨BRAF V600E基因突变对甲状腺乳头状癌（PTC）临床病理特征的影响。方法:收集经甲状腺切除术且病理证实为PTC患者的临床资料,分析BRAF V600E基因突变与PTC临床病理特征、甲状腺功能的关系。结果:PTC患者882例,发生BRAF V600E基因突变者722例（81.86%）,单因素分析显示,突变组癌灶多发、双侧、包膜外侵犯比例、复发危险度分层中/高危及TNM分期Ⅲ/Ⅳ期明显高于未突变组,差异均有统计学意义（均P＜0.05）;而淋巴结转移率、转移数目和直径均无统计学差异;突变组TPOAb、TGAb、TSH水平低于未突变组,差异均有统计学意义（均P＜0.05）,FT4、FT3水平无统计学差异（均P＞0.05）。分别行多因素Logistic回归分析显示:BRAF V600E基因突变与癌灶多发、包膜外侵犯显著相关（OR值分别为1.722、1.436,均P＜0.05）;原发癌灶直径>1 cm、BRAF基因突变、TGAb异常升高与PTC患者包膜外侵犯呈独立正相关（OR值分别为2.862、1.619、1.532,均P＜0.05）。结论:BRAF V600E基因突变的PTC易发多灶和包膜外侵犯,提示可能有不良预后;癌灶直径>1 cm、BRAF V600E基因突变及TGAb异常升高是PTC包膜外侵犯的独立危险因素。     

甲状腺乳头状癌BRAF V600E、NRAS、TERT基因的突变特征及其与临床病理特征的相关性

目的:探索甲状腺乳头状癌(papillary thyroid carcinoma,PTC)三种驱动基因BRAF V600E、NRAS和TERT基因突变与临床病理特征的相关性,旨在为甲状腺癌患者提供更精准的分子分型检测指导。方法:纳入2018年01月至2018年12月期间空军军医大学西京医院收治的接受BRAF V600E、NRAS、TERT三基因检测的PTC患者,回顾性收集患者的临床病理特征和三种基因突变状态资料,分析各基因的突变特点及其与临床病理特征的相关性。结果:本研究347例患者,BRAF V600E、TERT、NRAS基因突变率分别为89.3%、2.0%以及1.2%。TERT和NRAS基因的患者同时发现有BRAF V600E基因突变。BRAF V600E/NRAS或BRAF V600E/TERT双基因突变率为3.2%。双基因突变患者多发病灶占72.7%,病理分型非PTMC占72.7%,淋巴结转移率为81.8%。BRAF V600E/NRAS双基因突变患者均发现淋巴结转移,BRAF V600E/TERT双基因突变患者有71.4%（5/7）出现淋巴结转移。单因素分析结果显示,年龄、病灶数量、病灶位置以及淋巴结转移与基因突变相关（P均＜0.05）。结论:BRAF V600E基因在PTC中的突变率达89.3%,TERT、NRAS基因突变往往与BRAF V600E基因突变同时出现,双基因突变可能与PTC侵袭性相关。     

甲状腺结节穿刺标本中BRAF V600E突变检测的临床意义

背景与目的：在甲状腺乳头状癌（papillary thyroid carcinoma，PTC）中，BRAF V600E突变是迄今报道最多的基因突变。检测甲状腺穿刺细胞中的BRAF V600E突变有助于提高细针抽吸细胞学检查（fine-needle aspiration cytology，FNAC）诊断的准确性。本研究对甲状腺穿刺细胞液进行BRAF V600E突变检测，与术后组织病理学诊断结果进行比较，评估BRAF V600E突变的术前诊断价值。方法：回顾性分析2016年6月—2017年4月在复旦大学附属肿瘤医院就诊的563例甲状腺结节患者的B超引导下FNAC标本中的BRAF V600E突变结果，所有病例用QIAamp DNA Mini Kit提取DNA，并用突变特异性扩增系统（amplification refractory mutation system，ARMS）方法检测BRAF V600E突变。结果：563例患者的FNAC标本中，ARMS方法检测成功率为99.3%，男女比例为1.0∶3.7，平均年龄（45.0±0.9）岁。以组织病理学诊断作为金标准对209例接受手术治疗的患者进行诊断，细胞学诊断PTC的灵敏度为86.6%，特异度为100.0%；细胞学联合BRAF V600E诊断PTC的灵敏度为92.1%，特异度为100.0%。FNAC联合BRAF V600E检测的诊断准确率高于细胞学诊断。组织病理学诊断为PTC的患者中，有11例患者细胞学诊断未见肿瘤细胞，但BRAF V600E检测有突变，其中9例为微小PTC。结论：用ARMS方法检测FNAC标本中BRAF V600E基因突变，检测成功率高，是临床易于开展的术前辅助诊断方法。将细胞学诊断与BRAF V600E检测结果相结合，可提高PTC的检出率，提高术前诊断的准确率。     

BRAF V600E mutation and p27 kip1 expression in papillary carcinomas of the thyroid <or=1 cm and their paired lymph node metastases

BACKGROUND: BRAF(V600E) mutation and p27(kip1) expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas. METHODS: Tissue samples from 214 consecutive patients who underwent total or near-total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) 相似文献   

多模态超声及术前BRAF基因预测甲状腺微小乳头状癌颈部淋巴结转移的价值

目的:分析甲状腺微小乳头状癌（papillary thyroid microcarcinoma,PTMC）多模态超声特征,结合临床资料及术前BRAF V600E基因检测,探讨PTMC患者颈部淋巴结转移（cervical lymph node metastasis,CLNM）的高危因素及其预测价值。方法:回顾性分析烟台毓璜顶医院2021年7月至2022年8月经手术病理证实的106例PTMC患者（114个病灶）,术前均行常规超声、CEUS、SWE检查及BRAF V600E基因检测。根据术后病理分为颈部淋巴结未转移组和转移组,应用单因素及多因素分析PTMC患者CLNM的危险因素。结果:单因素分析显示,患者性别、病灶内钙化类型、病灶增强水平、峰值强度（PI）及弹性模量平均值(Eavg)在两组间差异具有统计学意义（P＜0.05）,BRAF基因突变差异无统计学意义（P=0.855）。多因素分析显示,男性患者、病灶内微钙化、超声造影呈等或高增强,CLNM风险更高（P＜0.05）,三者联合诊断的灵敏度(92.3%)及准确度(73.9%)均高于单一诊断,差异有统计学意义（P＜0.05）。结论:男性、微钙化、CEUS呈等或高增强可以独立预测CLNM,而术前BRAF基因突变结果并不能作为预测CLNM的危险因素。基于临床资料和多模态超声特征联合构建的临床预测模型在术前评估PTMC患者CLNM方面具有较高的灵敏度和预测效能,能为诊疗方案的制定提供有价值的参考。     

Time to re‐consider the meaning of BRAF V600E mutation in papillary thyroid carcinoma

The BRAF V600E mutation, resulting from the BRAFT1799A transversion, is the most common genetic mutation in papillary thyroid carcinoma (PTC), with a mean frequency close to 50% among all cases. A large number of studies in the past decade have tried to dissect the relevance and the function of the V600E mutation in controlling oncogenesis and progression of thyroid cancer. However, several works published in the latest years have provided new evidence, in partial conflict with the previous knowledge, suggesting the need of reconsidering the meaning of the BRAF V600E mutation in PTC. In this work, we attempt to discuss some of the most recent molecular, preclinical and clinical evidence to construct a more exhaustive model of function for the BRAF V600E in development, progression and therapeutic approach of thyroid cancer.     

甲状腺乳头状癌BRAF V600E基因突变 及相关蛋白的表达

背景与目的:BRAF V600E基因突变可作为甲状腺乳头状癌靶向治疗的靶点,因此检测患者BRAF基因状态对于能否应用靶向药物治疗具有重要意义.观察BRAF V600E基因突变及突变蛋白VE1在甲状腺乳头状癌中的表达情况,并分析其与甲状腺乳头状癌的临床病理特征及其预后的关系.方法:采用DNA测序法及免疫组织化学法分别检测108例甲状腺乳头状癌、54例甲状腺腺瘤和54例结节性甲状腺肿标本中BRAF基因突变及其相关蛋白VE1的表达.结果:108例甲状腺乳头状癌基因突变率为67.6%,VE1表达率为64.8%,与甲状腺良性病变相比差异有统计学意义(P<0.05),与临床病理参数间无相关性.结论:甲状腺乳头状癌BRAF V600E基因突变率和BRAF V600E蛋白表达水平增高,可以作为鉴别甲状腺良、恶性肿瘤的有效指标.免疫组织化学法检测甲状腺乳头状癌BRAF V600E蛋白的表达与其基因突变的一致性高,可间接有效地反映BRAF V600E基因突变的状态.BRAF V600E基因突变及突变蛋白的表达与甲状腺乳头状癌患者预后无关.     

Utility of BRAF protein overexpression in predicting the metastasis potential of papillary thyroid carcinoma

V-raf murine sarcoma viral oncogene homolog B1 (BRAF) is a significant member of the MAPK pathway, the point mutation (V600E) of which is a common genetic event in papillary thyroid carcinoma (PTC). Investigators showed that the variations in BRAF expression levels were independent of the V600E mutation. These variations were involved in the pathogenesis of thyroid carcinomas. This study evaluated the feasibility of BRAF, proliferating cell nuclear antigen (PCNA) and hMSH2 as markers for the prediction of the metastatic potential of PTC. Using immunohistochemistry, the expression of BRAF, PCNA and hMSH2 proteins was studied in 70 PTC and 29 nodular goiter (NG) tissues. The results indicated that i) the positive rate of BRAF, PCNA and hMSH2 expression in PTCs was significantly higher than that in NGs (P=0.000, P=0.000 and P=0.003, respectively), ii) the positive rate of BRAF expression in the lymph node metastasis (LNM) group was significantly higher than that in the non-LNM group (P=0.019), iii) the age at diagnosis of PTC patients with LNM was significantly older compared to that without LNM (P=0.021) and iv) the positive rate of BRAF expression significantly correlated with that of PCNA and hMSH2 expression (P=0.000 and P=0.019, respectively). In conclusion, BRAF, PCNA and hMSH2 overexpression appeared to be molecular events of PTC carcinogenesis. Older patients with BRAF overexpression appear to be a high-risk group for PTC metastasis. Detection of BRAF expression is likely to aid in the prediction of the metastatic potential of the carcinoma.     

甲状腺乳头状癌18F-FDG PET/CT显像葡萄糖代谢与BRAF突变的相关性研究

目的 评估甲状腺乳头状癌(Papillary thyroid carcinoma,PTC)患者¹⁸F-FDG PET/CT的最大标准摄取值(SUV_max)与BRAF突变的相关性。方法 回顾性分析我院在甲状腺切除术前接受¹⁸F-FDG PET/CT显像和活检的患者51例(平均年龄为49.3±12.9岁),病理诊断为PTC 48例,甲状腺滤泡状癌(Follicular thyroid carcinoma,FTC)3例。采用基因检测法检测BRAF V600E突变状态,半定量分析法测定甲状腺结节灶的SUV_max,分析患者临床资料包括性别、年龄、肿瘤大小和甲状腺球蛋白浓度与SUV_max之间的相关性;将患者分为BRAF V600E突变组和未突变组,分析比较两组间SUV_max值的差异。结果 在PTC患者中,33例患者肿瘤发生BRAF V600E突变,15例患者肿瘤未发生突变,BRAF V600E突变组的SUV_max显著高于未突变组(5.5±3.9 vs. 2.2±1.2,P=0.002);肿瘤直径≥1cm的患者的SUV_max明显高于肿瘤＜1cm(P＜0.05);甲状腺球蛋白浓度升高患者的SUV_max高于正常甲状腺球蛋白浓度的患者(P＜0.05);FTC组中未观察到BRAF V600E突变。结论 PTC患者携带BRAF V600E突变基因相对于未携带者具有更高的SUV_max值,不同肿瘤大小、血清甲状腺球蛋浓度的PTC患者SUV_max值存在统计学差异。     

Detection of BRAF V600E mutation and RET gene rearrangement in papillary thyroid carcinoma and their clinical significance

Objective To investigate the correlation between BKAF V600K mutation and RET gene rearrangement and clinical pathological factors in papillary thyroid carcinoma (ITC). Methods The samples from 180 FTC patients and 30 patients with other l>enign j>r malignant thyroid lesion as control from January K 2012 to January 2014 were collected. The surgical removal tumor tissues were used for D.N'A and KNA extraction, and the BRAF V600E mutation and'RET gene rearrangement were detected. The correlations letween BRAF V600E mutation ami RET gene rearrangement and sex, age, the primary focal size, thyroid capsule invasion, lymph node metastasis and the clinical stage were analyzed. Results The BRAF V600E mutation rale and the RET gene rearrangement rate in ITC group were 59.4 % (107/180) and 42.2 % (76/180), respectively, hut those were not found in control group. BRAF V600E mutation positive rates in different sex, age and primary tumor size had no statistical difference (P>0.05), whereas those in different thyroid extracapsular invasion (X2 = 5.46, P = 0.01), neck lymph node metastasis (X2 = 3.36, P 0.02) and clinical stage Or = 6.36, P=0.03) had statistical difference. Conclusions BRAF V600E mutation and RET gene rearrangement are related with extracapsular invasion, neck lymph node metastasis anil clinical stage HI-IV in PTC.     

甲状腺乳头状癌BRAFV600E基因突变与钠碘同向转运体表达的研究

目的:探讨甲状腺乳头状癌(PTC)患者中BRAFV600E基因突变及钠碘同向转运体(NIS)蛋白的表达及两者间的相关性.方法:收集2008-01-01—2011-01-01青岛大学医学院附属医院病理科PTC石蜡包埋组织30例,其中癌旁组织为正常组织(G正常组)15例,癌旁组织为结节性甲状腺肿组织(G结甲组)15例.对PTC组织行DNA提取、PCR扩增、基因测序检测BRAFV600E基因突变,同时采用免疫组化的方法分析NIS蛋白表达,结果以免疫组化评分(IHS)表示.结果:30例PTC均无BRAFV600E基因突变;30例PTC组织中NIS蛋白表达,从0～12分,G正常组IHS=(7.92±3.01)分,G结甲组IHS=(6.58±2.71)分,两组NIS差异无统计学1意义,t=1.11,P=0.95;BRAFV600E突变与NIS蛋白表达无相关性.结论:尚未发现癌旁不同的PTCBRAFV600E基因有突变及NIS蛋白表达的差异.BRAFV600E基因突变与NIS表达在PTC中的关系有待进一步研究.     

甲状腺乳头状微小癌颈部淋巴结转移的影响因素分析

目的:探讨甲状腺乳头状微小癌（PTMC）发生淋巴结转移（LNM）的影响因素。方法:收集535例行甲状腺切除术且病理证实为PTMC患者的临床资料,比较PTMC患者中有和无淋巴结转移、不同转移区域、不同肿瘤直径组间临床病理特征,分析淋巴结转移与临床病理特征的相关性。结果:PTMC合并淋巴结转移组192例（35.89%）,非淋巴结转移组343例（64.11%）,两组比较,淋巴结转移组年龄<55岁、男性、癌灶多发、双侧分布、直径>0.5 cm、合并桥本氏甲状腺炎（HT）、中/高危复发危险分层比例显著升高,差异均有统计学意义（均P＜0.05）;中央区淋巴结转移（CLNM）组147例（76.56%）,颈侧区淋巴结转移（LLNM）组45例（23.44%）,与CLNM组比较:LLNM组癌灶多发、双侧分布、合并HT比例升高,BRAF基因突变率比例降低,差异均有统计学意义（均P＜0.05）;肿瘤直径≤0.5 cm组187例（34.95%）,直径>0.5 cm组348例（65.05%）,与直径≤0.5 cm组比较:直径>0.5 cm组癌灶多发、双侧分布、合并LNM、包膜外侵犯、中/高危复发危险分层比例升高,差异均有统计学意义（均P＜0.05）;多因素Logistics回归分析显示年龄<55岁、男性、癌灶多发、直径>0.5 cm、合并HT是LNM的独立危险因素（均P＜0.05）。结论:年龄<55岁、男性、癌灶多发、直径>0.5 cm、合并HT是PTMC淋巴结转移的独立危险因素,颈部淋巴结转移增加PTMC复发风险。     

Notch1 receptor as a marker of lymph node metastases in papillary thyroid cancer

Notch functions as an oncogene or tumor suppressor according to the type of malignancy, and the BRAF(V600E) mutation is commonly observed in thyroid cancer. However, the role of Notch and BRAF(V600E) in papillary thyroid cancer (PTC) is unclear. This study sought to elucidate the clinicopathological characteristics in patients with PTC regarding the expression of Notch1/Notch3 receptors and BRAF(V600E) mutation. Clinicopathological characteristics were evaluated according to the Notch1/Notch3 receptors and BRAF(V600E) mutation in 187 patients with PTC who underwent definitive surgery. Expression of the Notch1 receptor was significantly associated with poor prognostic markers including large tumor size, nodal metastasis, capsular invasion, and extrathyroidal extension. However, there was no significant association between the clinicopathological characteristics and Notch3 receptor expression/BRAF(V600E) mutation. In multivariate analysis, Notch1 receptor expression showed a significant relationship with lymph node metastasis (P = 0.04). Notch1 receptor may be a predictor of lymph node metastasis and may be related to poor prognostic markers in patients with PTC. Further investigation of Notch1 receptor may further the understanding of the pathogenesis of nodal metastasis in PTC.     

The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose

In papillary thyroid carcinogenesis, the constitutively activated mitogen-activated protein (MAP) kinase signaling pathway caused by a genetic alteration such as RET/PTC rearrangement or mutation of RAS and BRAF genes, is thought to be a major early event. Among these, the recently identified BRAF(V600E) mutation has been found at high frequency in adult patients with papillary thyroid carcinoma (PTC). However, the association between this mutation and radiation exposure in adult PTC is still unknown. In this study, we examined the BRAF(V600E) mutation in 64 PTCs among adult atomic bomb survivors in Hiroshima, Japan, comprising 17 nonexposed (0 mGy) and 47 exposed patients who developed the carcinoma after the bombing, and assessed the association of BRAF(V600E) mutation with clinico-pathological and epidemiological variables. The median radiation dose in PTCs with the BRAF(V600E) mutation was significantly lower than that without the mutation (18.5 vs.156.9 mGy, Wilcoxon rank-sum test, P=0.022). A significant difference was found in the median latency period (years elapsed from atomic bombing to diagnosis) between exposed patients with and without BRAF(V600E) mutation (29 vs. 21 yr, Wilcoxon rank-sum test, P=0.014). These findings were further confirmed by logistic regression analysis with BRAF(V600E) mutation status as a dependent variable and taking into account possible interactions between the variables. We found that the log-transformed radiation dose and latency period were independently associated with the BRAF(V600E) mutation (P=0.039 and P=0.010, respectively). These results suggest that involvement of BRAF mutation in thyroid carcinogenesis in exposed people may differ from that in the nonexposed people.     

体质量指数与甲状腺乳头状癌临床病理特征的相关性分析

目的:分析体质量指数（body mass index,BMI）与甲状腺乳头状癌（papillary thyroid carcinoma,PTC）临床病理特征的相关性。方法:回顾性分析2017年1月至2018年6月于西京医院甲乳血管外科行手术的829例PTC患者临床资料,并将入组患者根据BMI的不同分为四组:较轻组（BMI＜18.5 kg/m2）、正常组（18.5≤BMI＜25 kg/m2）、超重组（25≤BMI＜30 kg/m2）及肥胖组（BMI≥30 kg/m2）。通过单因素分析及多元逻辑回归分析BMI与PTC临床病理特征相关性。结果:不同BMI组PTC患者的年龄、性别以及高血压病史之间具有统计学差异（P<0.001）。超重组患者与其他组相比平均年龄较大,肥胖组患者男性居多。单因素分析显示,BMI与肿瘤多灶性、BRAF V600E基因突变以及TNM分期显著相关（P<0.05）,而与病灶大小、病灶分布、是否侵犯包膜以及淋巴结转移数目和位置无关（P>0.05）。BMI正常组患者的肿瘤发生灶多为单灶（60.3%）,而非正常组患者多灶的发生率显著增加（P=0.040）。随着BMI的增长,BRAF V600E基因突变率显著提高（P=0.001）。经多元逻辑回归分析的校正,PTC患者的TNM分期与BMI无统计学差异（P>0.05）,肿瘤多灶性以及BRAF V600E基因突变仍与BMI显著相关。结论:在PTC患者中,非正常BMI组患者肿瘤多灶的发生率较正常BMI组显著增加,且BRAF V600E基因突变率与BMI呈正比,而除多灶性以外的侵袭性病理特征与BMI之间未发现相关性。     

BRAF基因V600E突变在甲状腺病变中的表达

目的 分析BRAF基因V600E突变在中国汉族人群甲状腺病变中的表达情况.方法 240例甲状腺病变中,乳头状癌(PTC)129例(其中经典型PTC 121例,滤泡型PTC 8例).滤泡癌12例,髓样癌4例,甲状腺隙瘤30例,结节性甲状腺肿30例,Lp状腺乳头状增生35例.采用常规酚.氯仿法抽提87例新鲜组织样本的总DNA,改良试剂盒法抽提153例石蜡组织样本的总DNA,经过PCR、测序,检测BRAF V600E突变.结果 在240例甲状腺病变中,BRAF V6OOE突变61例,发生率为25.4%.61例BRAF V600E突,变患者均为PTC,占PTC的47.3%.BRAF V600E突变在经典型PTC中的表达率(49.6%)与在滤泡型PTC中的表达率(12.5%)比较,差异有统计学意义(P<0.05).BRAF V600E突变与PTC患者临床病理参数间的差异无统计学意义(P>0.05).结论 BRAFV600E突变与PTC的发生、发展可能有着重要联系,BRAF V600E突变可以作为PTC诊断的特异性标记;改良的试剂盒法抽提石蜡组织DNA具有高效、简便、价格栩对低廉的优点.     

BRAF基因V600E突变在甲状腺病变中的表达

目的 分析BRAF基因V600E突变在中国汉族人群甲状腺病变中的表达情况.方法 240例甲状腺病变中,乳头状癌(PTC)129例(其中经典型PTC 121例,滤泡型PTC 8例).滤泡癌12例,髓样癌4例,甲状腺隙瘤30例,结节性甲状腺肿30例,Lp状腺乳头状增生35例.采用常规酚.氯仿法抽提87例新鲜组织样本的总DNA,改良试剂盒法抽提153例石蜡组织样本的总DNA,经过PCR、测序,检测BRAF V600E突变.结果 在240例甲状腺病变中,BRAF V6OOE突变61例,发生率为25.4%.61例BRAF V600E突,变患者均为PTC,占PTC的47.3%.BRAF V600E突变在经典型PTC中的表达率(49.6%)与在滤泡型PTC中的表达率(12.5%)比较,差异有统计学意义(P<0.05).BRAF V600E突变与PTC患者临床病理参数间的差异无统计学意义(P>0.05).结论 BRAFV600E突变与PTC的发生、发展可能有着重要联系,BRAF V600E突变可以作为PTC诊断的特异性标记;改良的试剂盒法抽提石蜡组织DNA具有高效、简便、价格栩对低廉的优点.     

BRAF基因V600E突变在甲状腺病变中的表达

目的 分析BRAF基因V600E突变在中国汉族人群甲状腺病变中的表达情况.方法 240例甲状腺病变中,乳头状癌(PTC)129例(其中经典型PTC 121例,滤泡型PTC 8例).滤泡癌12例,髓样癌4例,甲状腺隙瘤30例,结节性甲状腺肿30例,Lp状腺乳头状增生35例.采用常规酚.氯仿法抽提87例新鲜组织样本的总DNA,改良试剂盒法抽提153例石蜡组织样本的总DNA,经过PCR、测序,检测BRAF V600E突变.结果 在240例甲状腺病变中,BRAF V6OOE突变61例,发生率为25.4%.61例BRAF V600E突,变患者均为PTC,占PTC的47.3%.BRAF V600E突变在经典型PTC中的表达率(49.6%)与在滤泡型PTC中的表达率(12.5%)比较,差异有统计学意义(P<0.05).BRAF V600E突变与PTC患者临床病理参数间的差异无统计学意义(P>0.05).结论 BRAFV600E突变与PTC的发生、发展可能有着重要联系,BRAF V600E突变可以作为PTC诊断的特异性标记;改良的试剂盒法抽提石蜡组织DNA具有高效、简便、价格栩对低廉的优点.

Abstract：

Objective To evaluate the expression of BRAF V600E mutation in 240 Chinese patients with thyroid lesions. Methods Two hundred and forty Chinese patients with thyroid lesions, including 129 papillary thyroid carcinomas (PTC) , 12 follicular carcinomas, 4 medullary carcinomas, 30 adenomas, 30 nodular goiters, and 35 papillary hyperplasia. DNA was extracted from thyroid biopsy and paraffin embedded thyroid tissues, and the expression of BRAF V600E mutation was detected by polymerase chain reaction and DNA sequencing assays. Results The presence of BRAF V600E mutation was found in 61 of the total group of 240 cases (25. 4%). It was only detected in PTC (47. 3%), and not detected in other types of malignant and benign thyroid lesions. There was a statistically significant difference between the expression of BRAF V600E mutation in classic type PTC (49. 6% ) and in follicular type PTC (12. 5% ,P <0. 05) , but statistical data did not show any correlation between BRAF V600E mutation and clinicopathologic parameters in PTC (P > 0. 05). Conclusions BRAF V600E mutation has a significant correlation with PTC and the detection of BRAF V600E mutation may be used as an important prognostic marker of PTC. Our new method of DNA extraction from paraffin embedded tissues is efficient and inexpensive.     

cN0甲状腺微小乳头状癌多个淋巴结转移的危险因素分析

  目的  术后病理证实的淋巴结转移在临床淋巴结转移阴性（clinical lymph node negative,cN0）的甲状腺乳头状癌（papillary thyroid carcinoma,PTC）中并不罕见,本研究旨在探讨临床淋巴结转移阴性的甲状腺微小乳头状癌（papillary thyroid microcarcinoma,PTMC）淋巴结转移的危险因素,特别是多个淋巴结转移（>5枚）的危险因素。  方法  回顾性分析中国医学科学院北京协和医院2013年11月至2014年10月行手术的cN0 PTMC患者1 268例,其中男性270例,女性998例。分析患者的临床病理学特征,通过单因素、多因素分析寻找淋巴结转移及多个转移的风险因素。  结果  1 268例患者中共出现淋巴结转移416例（32.8%）,多个淋巴结转移43例（3.4%）,淋巴结转移的危险因素的单因素分析中,男性（42.22% vs. 30.26%,P < 0.01）、年龄 < 40岁（ < 40岁为48.39%,40~59岁为27.62%,年龄≥60岁为22.45%,P < 0.03）、多发病灶（41.00% vs. 29.03%,P < 0.01）、无慢性淋巴细胞性甲状腺炎（36.44% vs. 20.62%,P < 0.01）、肿瘤直径>0.5 cm（35.77% vs. 23.05%,P < 0.01）者淋巴结转移比例显著增加。多因素分析中,男性（OR=1.516,P < 0.001）、多发病灶（OR=1.743,P < 0.001）、肿瘤直径>0.5 cm（OR=1.788,P < 0.001）是淋巴结转移的独立危险因素;而年龄较大患者（40~59岁OR=0.388;60岁及以上OR=0.301,P < 0.001）、慢性淋巴细胞性甲状腺炎（OR=0.472,P < 0.001）是出现淋巴结转移的保护性因素。在多个淋巴结转移危险因素的多因素分析中,男性（OR=2.383,P=0.002）是多个淋巴结转移的独立危险因素;而年龄≥40岁则是保护性因素（OR=0.270,P < 0.001）。  结论  cN0 PTMC淋巴结转移并不少见,但是多个淋巴结转移少见,男性、年龄 < 40岁的患者淋巴结转移、多个转移的风险明显增加。