Surgical Perspective of T1799A BRAF Mutation Diagnostic Value in Papillary Thyroid Carcinoma

Background: Throughout Indonesia, thyroid cancer is one of the ten commonest malignancies, with papillarythyroid carcinoma (PTC) in our hospital accounting for about 60% of all thyroid nodules. Although fine needleaspiration biopsy (FNAB) is the most reliable diagnostic tool, some nodules are diagnosed as indeterminate andsecond surgery is common for PTC. The aim of this study was to establish the diagnostic value and feasibility oftesting the BRAF T1799A mutation on FNA specimens for improving PTC diagnosis. Materials and Methods: Thisprospective study enrolled 95 patients with thyroid nodules and future surgery planned. Results of mutationalstatus were compared with surgical pathology diagnosis. Results: Of the 70 cases included in the final analysis,62.8% were PTC and the prevalence of BRAF mutation was 38.6%. The sensitivity, specificity, positive predictivevalue (PPV), and negative predictive value (NPV) for BRAF mutation analysis were 36%, 100%, 100% and48%, respectively. With other data findings, nodules with “onset less than 5 year” and “hard consistency” wereproven as diagnostic determinants for BRAF mutation with a probability of 62.5%. This mutation was alsoa significant risk factor for extra-capsular extension. Conclusions: Molecular analysis of the BRAF T1799Amutation in FNAB specimens has high specificity and positive predictive value for PTC. It could be used in theselective patients with clinical characteristics to facilitate PTC diagnosis and for guidance regarding extent ofthyroidectomy.     

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.     

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。     

甲状腺乳头状癌经淋巴结转移规律及治疗策略

目的　探讨甲状腺癌的颈淋巴结转移规律及选择性颈淋巴结清扫术 ,应用于cN0 甲状腺乳头状癌病例的理论依据和应用原则。方法　前瞻性观察 3 0 0例甲状腺乳头状癌 ,分析cN0 pN (病理检查淋巴节阳性 )及cN pN 病例的颈淋巴结分布规律。结果cN pN 13 6例 ,cN0 pN 164例 ,颈淋巴结转移 2 5 1例 ,占 83 67% ,其中气管周围 2 2 8例 ,同侧Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ区分别为 1例、61例、2 41例、2 46例、5 9例 ;cN0 pN 115例 ,分布情况为气管周围 10 8例 ,同侧Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ区分别为 0例、5例、10 5例、10 9例、3例 ;结论甲状腺乳头状癌淋巴结转移最常见于气管周围、颈部同侧Ⅲ、Ⅳ区。选择性颈淋巴结清扫术对cN0 甲状腺乳头状癌具有重要治疗作用。     

Papillary Thyroid Carcinoma in Iceland: A study of the Occurrence in families and the coexistence of other primary tumours

This paper presents evidence from Iceland which indicates that papillary thyroid carcinoma occurs in certain families more often than expected. Thyroid carcinoma was also seen to coexist with some other cancer types more often than expected. We studied all families (n = 373) with papillary thyroid carcinoma diagnosed between 1955 and 1984 in Iceland. Familial papillary carcinoma occurrred in 3.8% of these families. This frequency was higher than expected but not significantly increased. Second primaries in women, and especially the incidence of kidney and breast cancer, were significantly increased. Cancer of the kidney and CNS tumours were significantly increased in propositi when both sexes were taken together. No increase in the incidence of other malignancies was observed in first degree relatives of patients with papillary thyroid carcinoma.     

Prophylactic Level VII Nodal Dissection as a Prognostic Factor in Papillary Thyroid Carcinoma: a Pilot Study of 27 Patients

Background: Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinomahas been highlighted. Materials and Methods: A total of 27 patients with papillary thyroid carcinoma with N0neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision.Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separateand independent prognostic factors for DFS at 24 months. Results: 21 females and 6 males with a mean ageof 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7),bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) andlevel VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-upfrom 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at24 months was 87.8% and was significantly affected in relation to bilaterality (p-value <0.001), extrathyroidalextension (p-value <0.001), level VI positive ((p-value <0.001) and level VII positive ((p-value <0.001) LNs. Norecurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement.Conclusions: Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillarythyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessityand safety of this approach.     

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.     

nm23基因在人甲状腺乳头状癌的表达及其与淋巴结转移的关系

应用免疫组化ＡＢＣ法检测１００例甲状腺乳头状癌标本中ｎｍ２３基因产物二磷酸核苷激酶（ＮＤＰＫ）的表达。结果总阳性率６７％，其中无淋巴结转移组阳性率８５％（３４／４０），伴有淋巴结转移组阳性率５５％（３３／６０）（Ｐ＜０．０１）；未侵犯包膜组阳性率７９％（３０／３８），侵犯包膜组阳性率６０％（３７／６２）（Ｐ＜０．０５），提示ｎｍ２３基因在甲状腺乳头状癌的表达与淋巴结转移及包膜侵犯呈负相关关系。结果还显示，在ｎｍ２３基因表达阳性的病例中，未侵犯包膜与侵犯包膜组淋巴结转移率分别是７％（２／３０）及８４％（３１／３７），（Ｐ＜０．０１），提示尽管ｎｍ２３阳性，侵犯包膜组明显比未侵犯包膜组淋巴结转移机会大；在未侵犯包膜的病例中，ｎｍ２３（－）及ｎｍ２３（＋）病例的淋巴结转移率分别是７５％（６／８）及７％（２／３０）（Ｐ＜０．０５），提示尽管未侵犯包膜，但在ｎｍ２３阴性时，淋巴结转移的可能性仍很大。结论：本检测有助于探讨代表甲状腺乳头状癌转移趋势的分子生物学标志，更科学地选择手术方式。     

Clinicopathologic and Diagnostic Significance of p53 Protein Expression in Papillary Thyroid Carcinoma

Background: p53 protein expression has been detected immunohistochemically in papillary thyroidcarcinoma(PTC). We investigated the relations between its expression and clinicopathologic features and itssignificance as a diagnostic marker. Materials and Methods: We compared and evaluated 93 patients in whomthyroidectomy with lymph node dissection had been performed to treat PTC for clinicopathologic significanceand 102 patients with 23 papillary thyroid overt carcinomas (POC), 57 papillary thyroid microcarcinomas(PMC),5 follicular adenomas (FA), 5 Hashimoto’s thyroiditis (HT) and 12 nodular hyperplasias (NH) for significanceas a diagnostic marker. Expression of p53 protein was evaluated immunohistochemically in sections of paraffinembeddedtissue. Results: Statistical analysis showed significantly different expression of p53 in PTC versusother benign thyroid lesions (BTL).The diagnostic sensitivity and specificity were 85.0% and 72.7%, respectively.Overexpression of p53 protein was observed in 44 of the 93 PTC cases (47.3%), but no significant correlationbetween p53 protein overexpression and clinicopathologic features (age, size, multiplicity, lymph node metastasis,extrathyroidal extension and vascular invasion) was noted. Conclusions: p53 is valuable to distinguish PTC fromother BTL, but there is no correlation between p53 protein overexpression and clinicopathologic features.     

MiR-125 b在甲状腺癌患者中的表达及其意义

目的 探讨miR-125b在甲状腺癌患者中的表达及其意义.方法 选取甲状腺乳头状癌组织及其配对的癌旁组织各20例,所有患者均经超声及病理确诊.实时荧光定量PCR检测miR-125b mRNA的表达,Western Blot检测Foxp3、LC 3I和LC 3II蛋白的表达.将人甲状腺乳头状癌细胞系MDA-T32随机分为...     

Risk Factors Associated with Thyroid Carcinoma in North Pakistan

Background: Epidemiological data on thyroid cancer and associated risk factors are scarce in our setting. The present study was therefore designed to gather data which could be helpful in providing insights to thyroid physicians and surgeons for better management of affected patients. Purpose: To determine the frequency of carcinoma thyroid among patients presenting with goiter and its association with TSH, Tg/ATg and other demographic factors. Materials and Methods: A total of 73 adult patients of either gender with solitary solid cold nodules and/or multi-ndoular goiter (MNG) with predominant solid cold nodules were enrolled. All surgically resected samples were sent for histopathology. The frequency of thyroid cancer and its subtypes was noted and tested for association with gender, age (< or ≥40 years), recent increase in swelling size, TSH, Tg and ATg. Results: Thyroid cancer was diagnosed in 26% (n=19) of the patients, 14 (73.7%) being diagnosed with papillary thyroid cancer and 5 (26.3%) with follicular thyroid cancer. No other subtypes were noted. Presence of thyroid cancer was significantly associated with recent increase in swelling size and higher TSH Values mean TSH values (P<0.05). No significant association was found with gender, age, Tg and ATg values (P>0.05). Conclusions: Overall percentage of thyroid cancer in our study sample was found to be 26%, with a predominance of papillary over follicular lesions. Rates were significantly higher in patients who had history of recent increase in swelling size and higher and higher pre-surgery TSH values.     

58例甲状腺髓样癌降钙素及其基因相关肽检测的临床意义

目的:探讨甲状腺髓样癌患者降钙素及其基因相关肽的变化规律以指导临床治疗方案的选择和患者预后的判断.方法:对58例甲状腺髓样癌患者血清中降钙素进行分析及应用免疫组织化学方法观察相应标本中降钙素及其基因相关肽的表达情况;对新入组患者进行放射免疫学测定.结果:1)术前降钙素水平正常与升高的患者之间,颈淋巴结转移存在显著性差异(P＜0.01).2)术后1个月降钙素水平正常与升高的患者之间,肿瘤复发存在显著性差异(P＜0.01).3)约98%的患者肿瘤标本降钙素染色呈阳性,而降钙素基因相关肽的阳性率为87.8%.4)部分术前降钙素水平正常的惠者降钙素基因相关肽水平升高.5)术后1周左右降钙素下降至一稳定水平.结论:降钙素可以作为指导甲状腺髓样癌诊断和治疗的重要指标,检测降钙素基因相关肽有助于部分降钙素阴性的甲状腺髓样癌患者术前诊断.     

The Role of Claudin-1 Expression in Follicular and Papillary Thyroid Neoplasm

Objective: This study evaluated differences in Claudin-1 expression between follicular adenoma (FA), follicular thyroid carcinoma (FTC), follicular variant papillary thyroid carcinoma (FV-PTC), and papillary thyroid carcinoma (PTC). Material and methods: This study used a cross-sectional approach. Immunostaining using the polyclonal antibody Claudin-1 was performed on 75 samples divided into 20 samples for follicular adenoma, follicular thyroid carcinoma, papillary carcinoma, and 15 samples of follicular variant thyroid carcinoma, respectively. Results: Claudin-1 expression is detected on the cytoplasmic membrane of tumor cells and appears to be varied among thyroid neoplasms. The claudin-1 expression score revealed a statistically significant difference between FA against FV-PTC, FA versus (vs) PTC, and FTC vs PTC, with median values of 4 vs 6 (p = 0.016), 4 vs 8 (p = 0.001), and 5 vs 8 (p = 0.002), respectively. However, there was no statistically significant difference in scores between the FA and the FTC (4 vs 5), or between the FTC and the FV-PTC groups (5 vs 6 (p=1,000). Conclusion: These results suggest that Claudin-1 may be capable of discriminating follicular adenoma from classic and follicular variant of papillary thyroid carcinoma. It can also differentiate follicular thyroid carcinoma and papillary thyroid carcinoma, especially for cases challenging to assess by hematoxylin and eosin staining. It still holds promise in providing targeted cancer therapy.     

甲状腺癌组织中H-ras基因突变及蛋白表达的预后价值

对５４例甲状腺癌标本分别用ＰＣＲ－ＲＦＬＰ法检测Ｈ－ｒａｓ基因第１２位密码子的突变及免疫组化法检测ｐ２１ｒａｓ蛋白，并用时序检验分析ｒａｓ基因突变和ｐ２１ｒａｓ蛋白表达与甲状腺癌的关系。结果发现，甲状腺癌中１８例（３３．３％）有ｒａｓ基因突变和４９例（９０．７％）有ｐ２１ｒａｓ蛋白过度表达。临床分期晚、分化程度低的甲状腺癌突变率较高，具有Ｈ－ｒａｓ原癌基因突变和ｐ２１ｒａｓ蛋白阳性的病例有较高的复发率和死亡率。表明ｒａｓ基因突变及其蛋白过度表达在甲状腺癌的发生和发展过程中发挥作用，是预后不良的标志     

Correlation of Contrast-Enhanced Ultrasonographic Features with Microvessel Density in Papillary Thyroid Carcinomas

Background: The purpose of this study was to investigate the correlation of contrast-enhanced ultrasonographic (CEUS) features with microvessel density (MVD) in papillary thyroid carcinomas (PTCs). Materials and Methods: Contrast-enhanced ultrasonography (CEUS) was performed in 62 patients (17 men and 45 women) with PTC. Tomtec software was applied to analyze the time intensity curve of CEUS. Immunohistochemistry was performed to evaluate the level of MVD in papillary thyroid carcinoma. Then the relationship between quantitative feature and the level of MVD was analyzed using SPSS 16.0 software. Results: The mean peak intensity of PTC tissues was lower than that of peripheral thyroid parenchyma (61.9±11.8% vs 100%, p<0.05). The MVDs of CD34 and CD31 antibodies staining were 38.0±6.1 and 37.9±5.1 respectively in 62 PTC samples.A significantly positive correlation was observed between peak intensity and MVD in PTC tissues (PCD34<0.01, rCD34=0.838, PCD31<0.01, rCD31=0.837). Conclusions: The peak intensity in CEUS could reflect the MVD in PTC tissues. Therefore, quantification of CEUS seems to be helpful for assessment of MVD in PTC tissues.     

Somatic Mutation of the APC Gene in Thyroid Carcinoma Associated with Familial Adenomatous Polyposis

We report the existence of both germline and somatic mutations of the APC gene in thyroid carcinomas from familial adenomatous polyposis (FAP) patients. One papillary thyroid carcinoma from a 20-year-old woman, with germline mutation of the APC gene (TCA to TGA at codon 1110), showed a somatic mutation of AAAAC deletion between codons 1060 and 1063. Another somatic mutation of CAG to TAG at codon 886 was also found in one of multiple thyroid carcinomas from a 26-year-old woman with attenuated FAP and germline mutation at codon 175 (C deletion). This is the first evidence that total absence of the normal function of the APC gene is involved in development of thyroid carcinomas in FAP.     

Clinical Features and Prognosis of Patients with Benign ThyroidDisease Accompanied by an Incidental Papillary Carcinoma

Purpose: To investigate the clinical features and prognosis of papillary thyroid carcinoma (PTC) with abackground of benign disease. Method: A total of 709 patients with papillary thyroid carcinoma undergoingsurgical resection were analyzed retrospectively. In 147 patients who underwent surgery for benign thyroiddisease, incidental PTC (IPC group) were identified by intraoperative or postoperative pathological examinationof surgical specimens but were not detected by preoperative imaging studies. In the other group, according tothe pathological examination with or without co-existing benign thyroid disease, 253 cases were clarified asconcomitant PTC and 309 cases were clarified as dominant PTC. Results: Incidental PTC was more commonin women, about 85.7%, the mean age was 47.6±11.3 years old. Average tumor diameter was 4.4±2.2 mm,multiple lesions accounted for 12.9% (19/147), and the cervical lymph node metastasis rate was 6.1% (9/147).After radical resection 8 cases recurred, the median time of recurrence was about 12 months (0.5 to 162), therewas no tumor-related death. The tumor-free survival rates were 97.3%, 95.9%, 91.5%, and 79.3% in 1, 5, 10and 14 year respectively. Conclusion: Incidental PTC with a background of benign lesions is common, and thegenerally good prognosis can be attributed to tumor early detection and early treatment. On the intraoperativefinding of incidental PTC, lobectomy (unilateral) or total thyroidectomy (bilateral) should be the first choice, butwith a postoperative pathologic finding of incidental PTC, further treatment, such as completion thyroidectomyor immediate lymph dissection is not necessary. Central lymph node dissection is also not needed unlesslymphadenectasis is present.     

甲状腺乳头状癌颈淋巴结转移途径

[目的]探讨甲状腺乳头状癌颈淋巴结可能的转移途径，及气管旁淋巴结与颈外侧淋巴结转移的相关性。[方法]回顾分析54例资料完整的甲状腺乳头状癌的临床及病理资料，分析颈部各区淋巴结转移率，比较气管旁淋巴结转移与颈外侧区淋巴结转移的关系。[结果]颈深上(Ⅱ区)、颈深中(Ⅲ区)、颈深下(Ⅳ区）、副神经区(V区）、气管旁(Ⅵ区)淋巴结转移率分别为25．9％、50．O％、59．3％、14．8％、70.4％，气管旁淋巴结转移者84．2％有颈外侧区淋巴结转移。气管旁淋巴结无转移者仅18．8％有颈外侧区淋巴结转移。[结论]气管旁是甲状腺乳头状癌颈淋巴结最常见转移部位，气管旁淋巴结转移与颈外侧区淋巴结转移有相关性。     

桥本甲状腺炎合并甲状腺癌患者肿瘤内抗肿瘤免疫临床意义

目的 观察桥本甲状腺炎合并甲状腺癌患者肿瘤内抗肿瘤免疫并探讨其临床意义.方法 应用免疫组织化学二步法检测桥本甲状腺炎合并甲状腺乳头状癌患者肿瘤组织内S-100蛋白呈阳性的树突状细胞及HLA-DR抗原呈阳性表达的细胞并探讨其临床意义.结果 桥本甲状腺炎合并甲状腺乳头状癌患者肿瘤组织内存在大量树突状细胞(8/8),数量明显多于不伴桥本甲状腺炎的甲状腺癌患者(1/20),树突状细胞的胞浆突起插入癌细胞之间并与之接触.癌细胞呈不同程度HLA-DR抗原阳性表达.在树突状细胞及HLA-DR抗原阳性表达的癌细胞间可见大量淋巴细胞围绕.癌细胞存在不同程度坏死、崩解、脱落.结论 桥本甲状腺炎合并甲状腺乳头状癌患者肿瘤组织内存在由树突状细胞、淋巴细胞及HLA-DR抗原阳性表达的癌细胞引起的特异性抗肿瘤免疫,与患者预后可能密切相关.