MicroRNA Expression Profiles in the Management of Papillary Thyroid Cancer

Papillary thyroid cancer (PTC) is the major contributor to the dramatically increasing incidence of thyroid cancer. Low‐risk PTC shows the most rapid rate of increase because of changing trends in neck imaging and the use of fine needle aspiration to investigate thyroid nodules. The need for a paradigm shift in the management of these patients, to provide personalized treatment and surveillance plans, has led to the focus on molecular biomarker research. MicroRNAs (miRNAs) compose a class of molecules with promising applications for every stage of PTC management, including diagnosis, prognosis, treatment, and surveillance. Although most of the miRNA studies are currently preclinical, given the rapid progress of scientific discovery, clinical trials will not be far away. Thyroid clinicians will be expected to have good insights into the current status of PTC‐related molecular translational research. This article focuses on the potential roles of miRNA in PTC management in the context of contemporary recommended clinical practice.     

BRAF Mutations in Iranian Patients with Papillary Thyroid Carcinoma

Background: Papillary thyroid cancer or papillary thyroid carcinoma (PTC) is the most common thyroidcancer. The fact that it occasionally occurs in women aged 30-40 years old suggests that genetic alterations areinvolved its genesis. Recently, activator mutations in BRAF gene have been relatively frequently discovered.Materials and Methods: In this study, we tested 63 DNA samples from PTC patients to identify the V600Emutation frequency in the Ahvaz population. DNA was isolated from formalin fixed paraffin-embedded (FFPE)PTC tumor tissues. Genotyping was performed by PCR-RFLP and confirmed by direct DNA sequencing of asubset of PCR products. PCR-RFLP data were reported as genotype frequencies and percentages. Results: Fortynine out of 63 patients (77.8%) had a mutated heterozygote form while 14 (22.2%) showed normal genotype butnone demonstrated a mutant homozygote genotype. The frequency of V600E mutation was significantly high inPTC patients. Conclusions: These findings support involvement of V600E mutations in PTC occurrence in Iran.Assessment of correlations between BRAF V600E mutations and papillary thyroid cancer progression needs tobe performed.     

长链非编码RNA在甲状腺乳头状癌中的研究进展

摘 要：甲状腺乳头状癌是最常见的内分泌腺恶性肿瘤,其发病率显著上升。lncRNA因其非编码性一直处于研究盲区,随着基因测序技术的逐渐成熟,lncRNA在表观遗传调控、转录调控、转录后调控的重要作用初步显现,探究lncRNA对于细胞生命活动的意义受到越来越多的关注。lncRNAs作为一类新的ncRNAs,在甲状腺乳头状癌细胞增殖,癌变和转移中起重要作用。其可作为甲状腺乳头状癌诊断、预后的生物标志物学和靶向治疗的潜在靶点。全文就lncRNA的结构功能、在甲状腺乳头状癌中的应用,以及作为治疗靶点进行综述。     

无区域淋巴结转移甲状腺乳头状癌患者的颈部处理

目的：探讨无区域淋巴结转移甲状腺乳头状癌患者选择性颈清扫的价值。方法：回顾分析424例无区域淋巴结转移甲状腺乳头状癌患者的临床资料,比较选择性颈清扫与否对生存效果的影响。结果：15年生存率选择性颈清扫组为83.0%,腺叶切除组为65.2%(P＜0.05);远处转移率选择性颈清扫组为6.8%,腺叶切除组为21.7%(P＜0.01).结论:选择性颈清扫将改善无区域淋巴结转移甲状腺乳头状癌患者的预后.     

Lymph Node Ratio Predicts Recurrence in Papillary Thyroid Cancer

Background.

Lymph node metastasis occurs in 20%–50% of patients presenting for initial treatment of papillary thyroid cancer (PTC). The significance of lymph node metastases remains controversial, and the aim of this study is to determine how the lymph node ratio (LNR) may predict the likelihood of disease recurrence.

Methods.

We conducted a retrospective review of patients undergoing total thyroidectomy for PTC at our institution from 2005 to 2010. A total LNR (positive nodes to total nodes) and central lymph node ratio (cLNR) was calculated. Regression was used to determine a threshold LNR that best predicted recurrence. Multivariate logistic regression then determined the influence of LNR on recurrence while accounting for other known predictors of recurrence. Kaplan-Meier analysis and the log-rank test were used to compare differences in disease-free survival.

Results.

Of the 217 patients undergoing total thyroidectomy for PTC, 69 patients had concomitant neck dissections. Sixteen (23.2%) patients developed disease recurrence. When disease-free survival functions were compared, we found that patients with a total LNR ≥0.7 (p < .01) or a cLNR ≥0.86 (p = .04) had significantly worse disease-free survival rates than patients with ratios below these threshold values. Considering other known predictors of recurrence, we found that LNR was significantly associated with recurrence (odds ratio: 19.5, 95% confidence interval: 4.1–22.9; p < .01).

Conclusions.

Elevated total LNR and cLNR are strongly associated with recurrence of PTC after initial operation. LNR in PTC is a tool that can be used to determine the likelihood of the patient developing recurrent disease and inform postoperative follow-up.     

基线刺激甲状腺球蛋白水平在预测甲状腺乳头状癌131I“清甲”疗效的价值

摘 要：［目的］ 探讨甲状腺乳头状癌术后TSH刺激状态下甲状腺球蛋白（STg）水平预测131I清甲疗效的价值。［方法］回顾性分析首次131I清甲治疗的138例甲状腺乳头状癌患者资料,其中男性35例,女性103例,中位年龄（45.69±11.93）岁,分析基线STg水平对清甲成功（清甲后6~12个月STg＜1ng/ml 、DxWBS未见甲状腺床摄碘、颈部超声未见甲状腺残留）的预测价值。［结果］ 总清甲成功率为73.9%（102/138）,清甲成功组与失败组基线STg值分别为（7.82±10.57）ng/ml、（57.97±97.56）ng/ml,两者具有统计学差异（t=-5.14,P＜0.001）,采用ROC曲线分析STg截断值为12.8ng/ml,当STg≤12.8ng/ml时,其预测清甲成功的灵敏度、特异性、阳性预测值、阴性预测值分别为63.89%、83.33%、91.56%、44.90%,结果显示86.6%(84/97)STg≤12.8ng/ml患者和43.9%(18/41)STg＞12.8ng/ml患者清甲成功。［结论］ 甲状腺乳头状癌术后131I治疗前TSH刺激下Tg水平是一个可靠的预测清甲疗效的指标。     

Urinary Neopterin Levels in Patients with Thyroid Cancer

Increased urinary neopterin concentrations have been described in many cancers. We aimed to evaluate the urinary neopterin levels in thyroid cancer. Sixty-nine patients with thyroid cancer, 76 patients with benign thyroid pathology and 33 healthy subjects were evaluated. First morning urine samples were collected from the patients and normal subjects for neopterin and creatinine measurement and stored at −80 °C until analysed. Neopterin levels were 149.3 (15.2–1,602.2) μmol/mol creatinine in the malignant group, 32 (5.2–275.6) μmol/mol creatinine in the benign group and 9.2 (2.7–78.7) μmol/mol creatinine in normal subjects (p ≤ 0.001). Urinary neopterin levels were significantly higher in patients with thyroid cancer than patients with benign thyroid pathologies and normal subjects. Also the patients with benign thyroid pathologies had a higher urinary neopterin level than the normal subjects. Malignant group was divided to two groups; patients with/without chronic thyroiditis (confirmed histologically). There were 22 (31.9 %) patients with and 47 (68.1 %) patients without chronic thyroiditis. Urinary levels of neopterin didn’t differ in both groups (168.6 (21.3–716.8) μmol/mol creatinine and 135.3 (15.2–1,602.2) μmol/mol creatinine respectively; p = 0.381). Urinary neopterin levels are high in thyroid cancer patients independently from the presence of chronic thyroiditis.     

pN1期甲状腺乳头状癌术后复发危险因素分析

摘 要：［目的］ 探讨pN1期甲状腺乳头状癌术后复发的危险因素。［方法］回顾性分析380例手术pN1期甲状腺乳头状癌患者的临床病理特征,及其与术后复发的关系。［结果］380例患者中术后20例（5.3%）出现肿瘤复发,复发时间10.9±5.2个月。单因素分析显示多发病灶、被膜外侵犯、转移淋巴结数＞5个以及淋巴结转移率≥0.4与肿瘤复发有关（P＜0.05）,而年龄、性别、原发肿瘤大小、是否为双侧病变、是否合并慢性淋巴细胞性甲状腺炎以及BRAFV600E基因突变与肿瘤复发无关（P＞0.05）。多因素分析显示,被膜外侵犯和淋巴结转移率≥0.4是肿瘤复发的独立危险因素（P＜0.05）。复发患者中,复发部位以Ⅱ区淋巴结最为常见,Ⅵ区淋巴结和残余腺体少见。［结论］被膜外侵犯、淋巴结转移率≥0.4与肿瘤复发有关,此类患者术后需加强随访。术前需要加强对Ⅱ区淋巴结的评估。     

趋化因子受体CXCR4在甲状腺乳头状癌的表达及临床意义

目的:探讨趋化因子CXCR4在甲状腺乳头状癌中的表达及其与临床病理学参数的相关性.方法:利用半定量RT-PCR和免疫组织化学法分别检测72例新鲜甲状腺乳头状癌组织及52例甲状腺乳头状癌石蜡标本中CXCR4mRNA及蛋白的表达情况.结果:甲状腺乳头状癌组织中CXCR4mRNA及蛋白的阳性表达率分别为77.8%(56/72)、76.6%(95/124),而甲状腺良性病变组织及正常甲状腺组织均无表达,差异具有统计学意义(P＜0.01);在甲状腺乳头状癌组织中,CXCR4mRNA表达与蛋白表达成正相关关系(r=-0.714,P＜0.01).单因素分析显示CXCR4的蛋白表达与年龄、性别、肿瘤大小无关(P＞0.05),但与肿瘤侵犯程度、淋巴结转移、远处转移、临床分期密切相关(P＜0.05),且CXCR4蛋白阳性表达组的预后显著差于CXCR4蛋白阳性表达组(P＜0.05).结论:CXCR4阳性表达的甲状腺乳头状癌具有较高侵袭转移潜能,是预后不良的指标之一,CXCR4可作为抑制甲状腺乳头状癌侵袭转移的有效靶点.     

甲状腺乳头状癌颈侧区清扫术治疗现状

甲状腺乳头状癌容易发生颈部淋巴结转移,侧颈部是常见受累部位之一.颈部清扫术是治疗甲状腺癌颈转移的标准手段,但其清扫范围存在争议,应视颈部淋巴结转移的不同区域而定.广泛的侧颈部转移,建议治疗性的改良根治性颈清扫;颈部淋巴结转移不广泛者,特别是术前影像学检查或查体未发现ⅡB区和ⅤA区转移者,建议行ⅡA、Ⅲ、Ⅳ、ⅤB区的择区性颈清扫;cN0患者不主张行预防性颈清扫术.建议同时采用cN分期和pN分期来区别对待颈部淋巴结.     

合并乳腺癌的甲状腺癌152例临床病理学特征分析

摘 要：［目的］ 探讨有乳腺癌病史的甲状腺癌患者的临床病理学特征。［方法］ 回顾性分析浙江省肿瘤医院2006～2016年间收治的合并乳腺癌的152例甲状腺癌患者的临床病理资料。152例患者均为女性,中位年龄50（28~74）岁,中位随访时间36（9~115）个月。［结果］共5例出现复发转移（3例远处转移,2例局部转移）,共2例因乳腺癌死亡。同时性多原发癌TC=BC组37例,异时性多原发癌甲状腺癌首发TC１→BC２组16 例,异时性多原发癌乳腺癌首发BC１→TC２组99例。BC1→TC2组与TC2控制对照组淋巴结转移率（39.39% vs 28.28%,P=0.039）、是否微小癌（76.77% vs 65.99%,P=0.048）差异有统计学意义;152例患者中超重组患者（BMI＞24kg/m2,n=50）的肿瘤大小、甲状腺被膜侵犯率均高于正常体重组患者（BMI≤24kg/m2,n=102）,差异均有统计学意义（P=0.048,P=0.029）。［结论］ 乳腺癌首发的甲状腺癌患者淋巴结转移率更高,尤在超重患者中肿瘤更具侵袭性。对此类患者术前应详细评估可疑淋巴结再拟定手术方案,术中应仔细探查中央区淋巴结转移情况,必要时行侧颈淋巴结清扫。     

甲状腺乳头状癌与乳头状增生的免疫组化特征

目的 探讨甲状腺良恶性乳头状病变组织中细胞角质蛋白19(CK19)、半乳凝素-3(Gal-3)、HBME-1的表达及其鉴别诊断价值.方法 应用免疫组化S-P法检测CK19、Gal-3、HBME-1在46例甲状腺乳头状癌、30例结节性甲状腺肿伴乳头状增生、30例癌旁正常滤泡组织中的表达情况.结果 CK19、Gal-3、H...     

分化型甲状腺癌患者不同手术方式相关并发症的研究

目的分析分化型甲状腺癌患者不同手术方式相关并发症发生情况。方法回顾性分析68例甲状腺癌患者的临床资料,观察分化型甲状腺癌患者不同手术方式相关并发症发生情况。结果单纯甲状腺全切术与甲状腺全切+淋巴结清扫术喉返神经损伤及低钙血症发生率比较差异无统计学意义(P>0.05);单纯甲状腺全切术及甲状腺全切+淋巴结清扫术喉返神经损伤、低钙血症发生率,均显著高于腺叶及峡部切除术和腺叶及峡部切除术+对侧大部切除术(P<0.05);腺叶及峡部切除术与腺叶及峡部切除术+对侧大部切除术并发症发生率比较差异无统计学意义(P>0.05)。结论对于分化型甲状腺癌,手术切除范围越大,其喉返神经损伤及低钙血症的发生率就越高。     

青少年甲状腺癌患者的生存状况分析

目的：分析青少年甲状腺癌患者的生存状况及影响患者生存率和生存时间的因素。方法选择接受手术治疗的青少年甲状腺癌患者62例。统计患者的生存率和生存时间,应用Log-rank检验及Cox模型分析影响患者生存状况的因素。结果62例青少年甲状腺癌患者术后随访时间为60～106个月,半数无病生存时间为92个月,3年无病生存率为91．94％,5年无病生存率为85．48％,10年无病生存率为77．42％。影响青少年甲状腺癌患者术后生存状况的相关因素：性别、原发灶大小、包膜外侵犯、T分期、淋巴结转移、远处转移、手术方式、131 I治疗、临床分期。 Cox比例风险回归模型显示,包膜外侵犯、远处转移、手术方式和临床分期这4个因素均是影响青少年甲状腺癌患者术后生存状态的的独立因素。结论包膜外侵犯、远处转移、手术方式和临床分期是影响青少年甲状腺癌患者术后生存状况的独立因素,患者应尽早确诊,积极进行手术治疗,以提高生存率。     

甲状腺乳头状癌中央区淋巴结清扫的临床意义

[目的]探讨临床颈淋巴结阴性(CN0)的甲状腺乳头状癌中央区淋巴结清扫的临床意义.[方法]对2010年1月至2011年6月收治的178例CN0甲状腺乳头状癌患者行中央区淋巴结清扫,其中67例同期行外侧区淋巴结清扫.评估中央区淋巴结清扫术的安全性,并对中央区及外侧区淋巴结转移相关因素进行分析.[结果]中央区淋巴结清扫没有明显增加手术并发症.中央区淋巴结转移率为44.4％;中央区淋巴结转移率与肿瘤大小有关,外侧区淋巴结转移率与中央区淋巴结阳性数目有关.[结论]中央区淋巴结清扫是一个方便安全的手术,能使部分患者免除外侧区颈清扫,应列为CN0甲状腺乳头状癌患者的常规选择.     

甲状腺乳头状癌mir-221表达与BRAF突变的相关性研究

[目的]探讨甲状腺乳头状癌(PTC)中mir-221表达和BRAF基因状态的相关性和临床意义。[方法]采用RNA核酸印迹(Northern blot)法检测43例PTC癌组织及其癌旁正常组织中mir-221表达,直接测序法检测PTC癌组织中BRAF基因状态,分析mir-221表达和BRAF基因状态的相关性及其与临床病理特征的关系。[结果]mir-221在PTC癌组织中的表达显著高于配对正常组织(中位值:0.855vs0.549,P<0.001);mir-221高表达与临床分期(P=0.002)及淋巴结转移(P=0.042)有关。BRAF基因在PTC癌组织中的突变率为53.49%(23/43)。突变型BRAF的甲状腺癌患者组mir-221表达显著高于野生型BRAF患者组(P=0.024)。[结论]mir-221与BRAF基因在PTC的发生、发展过程中起重要作用,mir-221表达升高与BRAF基因突变有一定相关性。     

甲状腺乳头状癌与甲状腺结节钙化的关系研究

[目的]探讨甲状腺结节合并钙化与甲状腺乳头状癌的关系。[方法]回顾性分析240例甲状腺结节患者的彩色超声资料与病理诊断结果。[结果 ]240例甲状腺结节中,甲状腺良性疾病钙化率为23.3%（38/163）,而甲状腺乳头状癌中钙化率达75.3%（58/77）,两组差异有统计学意义（χ2=58.947,P〈0.001）。钙化诊断甲状腺乳头状癌的ROC曲线下面积为0.811（95%CI：0.750~0.871）。微钙化患甲状腺乳头状癌的风险是非微钙化者的5.348倍（95%CI：2.804~10.200）,而粗钙化患甲状腺乳头状癌的风险是非粗钙化者的4.000倍（95%CI：1.564~10.230）。[结论]钙化尤其是微钙化对于诊断甲状腺癌的特异性较高。当彩超发现甲状腺结节中有微小钙化时应提高警惕,尤其是微钙化,应进一步做针吸细胞学检查。