甲状腺乳头癌的蛋白质组学研究进展

甲状腺癌是最常见的内分泌系统恶性肿瘤,其发病率逐年上升,但甲状腺癌的术前准确诊断依然存在挑战。蛋白质组学的发展为甲状腺癌的研究提供了有力的手段,为甲状腺癌的发病机制探讨、早期诊断及疗效评价开辟新的思路,甲状腺乳头状癌(PTC)是最常见的甲状腺癌。目前PTC的蛋白质组学研究仍然有限,本文详细介绍PTC的蛋白质组学研究的进展。     

染色体重排与分化型甲状腺癌的发病机制

甲状腺癌是最常见的内分泌系统恶性肿瘤,发病率呈逐年上升趋势。2007年美国报道新发33500例,死亡1500例,而同一期其他内分泌恶性肿瘤仅为2000例,死亡800例。甲状腺癌中最常见的为分化型甲状腺癌（主要是甲状腺乳头状癌,Papillary thyroid carcinoma,PTC和甲状腺滤泡状癌,Follicular thyroid carcinoma,FTC）,大约占全部甲状腺癌的80％-90％。其中PTC占绝大多数,但死亡患者中却有40％是Frc。     

染色体重排与分化型甲状腺癌的发病机制

甲状腺癌是最常见的内分泌系统恶性肿瘤,发病率呈逐年上升趋势.2007年美国报道新发33500例,死亡1500例,而同一期其他内分泌恶性肿瘤仅为2000例,死亡800例[1].甲状腺癌中最常见的为分化型甲状腺癌(主要是甲状腺乳头状癌,Papillary thyroid carcinoma,PTC和甲状腺滤泡状癌,Follicular thyroid carcinoma,FTC),大约占全部甲状腺癌的80%-90%.其中PTC占绝大多数,但死亡患者中却有40%是FTC.     

BRAF V600E突变对甲状腺乳头状癌发生及预后的影响

甲状腺乳头状癌(papillary thyroid cancer,PTC)是甲状腺癌最常见的病理类型.PTC通常预后良好,但近年来甲状腺癌的发病率逐年攀升.随着患病人数的不断增多,中晚期难治性甲状腺癌患者不再少见.因此,越发庞大的甲状腺癌患者群体的管理与诊治已成为巨大的考验.BRAF V600E基因突变是乳头状癌经典DNA相关标志物,目前已被广泛应用于甲状腺癌的术前诊断和预后评估,并且作为潜在的治疗靶点受到越来越多的关注.因此,正确全面的了解BRAF V600E基因突变可以帮助我们对PTC的发生、发展及生物学行为有更进一步的了解,并为PTC患者管理方式与治疗策略提供新的方向.     

微淋巴管形成因素在甲状腺乳头状癌中的研究进展

甲状腺癌是内分泌最常见的恶性肿瘤,近年许多资料显示甲状腺癌在全球发病率有逐年上升趋势,每年增长约4%,甲状腺乳头状癌（papillary thyroid carcinoma,PTC）是其最常见的病理类型,并以颈部淋巴结转移为主。众多研究表明,淋巴结转移与肿瘤周围的微淋巴管形成密切相关。     

分化型甲状腺癌相关基因研究进展

<正>甲状腺癌是头颈外科及内分泌科最常见的恶性肿瘤,近年来在我国其发病率有上升趋势。2012年,甲状腺癌发病率为6.56/10万人。分化型甲状腺癌(differentiated thyroid carcinoma,DTC)起源于滤泡上皮细胞,是甲状腺癌中最常见的病理组织类型,占甲状腺恶性肿瘤的90%以上,其又分为乳头状癌(papillary thyroid carcinoma,PTC)和滤泡状癌(follic     

Galectin-3和MMP-9在甲状腺癌鉴别诊断中的研究进展

甲状腺癌是头颈部最常见的恶性肿瘤之一，其侵袭和转移是造成甲状腺癌患者死亡的主要原因。甲状腺癌从病理上主要分为乳头状甲状腺癌（PTC）、滤泡状甲状腺癌（FTC）、未分化甲状腺癌（UTC）和髓样甲状腺癌（MTC）等，但是当良性病变如结节性甲状腺肿、甲状腺炎、甲状腺腺瘤伴有乳头状生长时，其良、恶性鉴别诊断一直是病理诊断的难点。另外，各型甲状腺癌的术后治疗方案与肿瘤转移与否关系密切。因此，检测恶性甲状腺肿瘤标志物结合对肿瘤浸润转移能力的评估，有助于甲状腺癌的早期诊断、鉴别诊断及治疗方案的选择。     

基于质谱的高通量蛋白质组学技术对甲状腺癌精准诊疗的推动

甲状腺癌是常见的内分泌恶性肿瘤,发病率逐年增加。深入了解甲状腺癌发生发展机制对提高诊断准确性、进行精准风险分层和实现个性化治疗至关重要。近年来,随着质谱相关技术的不断发展,基于不同标本类型（细胞、组织、血清和尿液）的多种蛋白质组学分析方法已被广泛应用于甲状腺癌的研究中,从阐明发病机制、诊断分型、预测预后和靶向治疗等方面积极地推动了甲状腺癌精准诊疗的发展。     

甲状腺癌免疫治疗的研究进展

摘 要：甲状腺癌是内分泌系统中最常见的恶性肿瘤,其组织学类型主要有乳头状癌(PTC)、滤泡状癌(FTC)、髓样癌(MTC)和未分化癌(ATC)4种病理类型,其中PTC是最常见的一种类型,约占85%。近年来,甲状腺癌的发病率呈逐年快速上升趋势。目前,手术、内分泌治疗、核素内放疗是分化型甲状腺癌的三大治疗手段,总体效果良好。但部分甲状腺癌,如碘抵抗远处转移分化型甲状腺癌、低分化癌、未分化癌、远处转移髓样癌等难治性甲状腺癌,预后不良且治疗手段匮乏。免疫治疗近年来逐渐成为研究热点,甲状腺癌的免疫治疗有望成为治疗这部分复杂病例的一种新方法。目前应用于甲状腺癌的免疫治疗方法主要有肿瘤疫苗治疗,免疫检查点抑制剂治疗,过继免疫细胞治疗,单克隆抗体治疗和免疫调节细胞靶向治疗等。     

桥本甲状腺炎合并乳头状甲状腺癌的研究进展

<正>桥本甲状腺炎(Hashimoto's thyroiditis,HT)是免疫系统功能紊乱,介导攻击自身组织的免疫反应,临床表现为甲状腺组织肿大或结节,血液检测出TGAb、TPOAb等抗体。甲状腺癌常见病理类型包括:乳头状癌、髓样癌、滤泡癌和未分化癌等,其中以乳头状癌(papillary thyroid carcinoma,PTC)最常见。HT可合并甲状腺癌,其中主要是甲状腺乳头状癌。现就其流行病学、临床与组织病理学特点、发病机制、诊断、治疗及预后等做一论述。     

免疫组化染色在甲状腺乳头状癌诊断中的应用

甲状腺乳头状癌(papillary thyroid carcinoma,PTC)是最常见的起源于甲状腺上皮细胞的恶性肿瘤.大部分PTC可以通过光镜诊断,但是有些肿瘤缺乏典型病理学表现,需要采用免疫组化或遗传学等方法进行辅助诊断.目前由于分子遗传学诊断有限,免疫组化自然就成为了组织学形态之外的最重要的辅助手段.因此,寻找有效的生物标记物对于正确诊断至关重要,本文将就PTC的诊断标记物进行汇总,对正确选择相关抗体协助病理诊断提供帮助.     

甲状腺乳头状癌相关基因

甲状腺乳头状癌(PTC)的发生、发展与BRAF基因、RET原癌基因等多种基因的异常表达相关.研究提示基因突变在甲状腺癌的诊断、治疗以及预后的评估等各个方面存在很大的临床应用价值,基因诊断和基因治疗有望进入临床.     

Childhood thyroid carcinoma with BRAFT1799A mutation shows unique pathological features of poor differentiation

The prevalence of BRAFT1799A mutation in papillary thyroid carcinomas (PTCs) displays a marked age association: relatively high in adults and exceedingly low in childhood. We report a case of a 12-year-old Japanese female with PTC, the only one case that harbored BRAFT1799A mutation in a series of 46 childhood thyroid cancer tissues. On histology, the findings were so atypical that pathologists had repeatedly examined tumor sections to agree on the diagnosis of poorly differentiated follicular carcinoma. Upon molecular investigation, BRAFT1799A was detected in DNA extracted from paraffin-embedded material, whereas TP53 was wild-type. Since BRAFT1799A is strictly limited to PTCs, immunohistochemical staining for CD15, a specific marker for papillary carcinoma, was performed to verify the diagnosis. A small tumor area with papillary-like structure was stained positive. These findings strongly suggest that this case is a poorly differentiated carcinoma that arose from PTC and implies a possible association of BRAF mutation with dedifferentiated phenotype of PTCs.     

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.     

甲状腺乳头状癌组织中DAPK1与RARβ的表达及临床意义

目的：通过检测新疆地区甲状腺乳头状癌组织及甲状腺良性病变组织中DAPK1和RARβ的蛋白表达特点,探讨其在甲状腺乳头状癌发生发展中的意义。方法：采用免疫组织化学S-P法,检测DAPK1与RARβ在新疆地区38例甲状腺乳头癌、21例甲状腺良性腺瘤、13例桥本氏甲状腺炎、6例结节性甲状腺肿和6例癌旁正常甲状腺组织中的蛋白表达,并分析其与临床病理因素间的关系。结果：DAPK1在甲状腺乳头状癌中的阳性表达明显低于甲状腺腺瘤、桥本氏甲状腺炎、结节性甲状腺肿和癌旁正常甲状腺组织（P〈0.01）;RARβ在甲状腺乳头状癌中的阳性表达明显高于在甲状腺良性腺瘤、桥本氏甲状腺炎、结节性甲状腺肿和癌旁正常甲状腺组织（P〈0.01）;DAPK1与RARβ在甲状腺乳头状癌中的表达与患者的年龄、性别、民族无明显相关关系（P〉0.05）。结论：DAPK1可能参与了甲状腺乳头状癌的发生发展过程。检测DAPK1和RARβ的表达水平可作为判断甲状腺乳头状癌转移和预后的参考指标。     

Thyroid cancer

Four types of thyroid cancer comprise more than 98% of all thyroid malignancies. Papillary thyroid carcinoma (PTC) may have a very benign course while undifferentiated thyroid carcinoma (UTC) belongs to the most aggressive human malignancies. A variety of genes have been identified to be involved in the pathogenesis of thyroid carcinoma. Somatic Ras mutations seem to be an early event and are frequently found in follicular thyroid carcinomas. Somatic rearrangements of RET and TRK are almost exclusively found in PTC and may be found in early stages. Germline RET missense mutations lead to hereditary medullary thyroid carcinoma (MTC). In contrast, the significance of somatic RET mutations in sporadic MTC is unknown. p53 seems to play a crucial role in the dedifferentiation process of thyroid carcinoma. The precise role of PTEN remains to be elucidated. The only clearly identified exogenous factor that may lead to thyroid carcinoma (mainly PTC) is radiation. Of interest, radiation is capable to induce RET rearrangements. In general, early diagnosis is mandatory to enable the chance of cure. Surgery is the treatment of choice. Depending on the tumour type, surgery in combination with either radioiodine, external radiation or chemotherapy often enables the control of local tumour burden. In MTC and UTC, once thyroid cancer is spread to distant organs, efficacious therapeutic agents are almost non-existing. However, our growing knowledge of genes involved in thyroidal oncogenesis may contribute to the development of more effective treatment modalities. Some preliminary data on gene therapy are quite promising.     

Inflammation in thyroid oncogenesis

It is commonly accepted that cancer is linked to inflammation. The possible mechanisms by which inflammation can contribute to carcinogenesis include induction of genomic instability, alterations in epigenetic events and subsequent inappropriate gene expression, enhanced proliferation of initiated cells, resistance to apoptosis, aggressive tumor neovascularization, invasion through tumor-associated basement membrane and metastasis. Inflammation also affects immune surveillance and responses to therapy. In this review, we overview the current understanding of different aspects of thyroid cancer and inflammation. Several studies have strongly suggested an increased risk of PTC in patients with Hashimoto's thyroiditis (HT), the most common autoimmune disease in thyroid cancer. Furthermore, an intense immune infiltrate is often associated with papillary thyroid carcinoma (PTC), and might play a critical role in the regulation of carcinogenesis and in carcinoma progression. The characterization of the most relevant inflammatory pathways of cancer-related inflammation (CRI) is instrumental for the identification of new target molecules that could lead to improved diagnosis and treatment.     

甲状腺乳头状癌合并桥本氏甲状腺炎的临床病理特征

目的：研究合并桥本氏甲状腺炎对甲状腺乳头状癌的临床与病理特征的影响。方法：对我院848例首次手术治疗并经病理确诊为甲状腺乳头状癌的病例进行回顾性分析,按病理是否诊断桥本氏甲状腺炎分为观察组（合并桥本氏甲状腺炎）与对照组（非合并桥本氏甲状腺炎）,分析比较两组间临床病理特征的差异。结果：观察组女性比例更高（95.6% vs 80.6%,P <0.01）,血清甲状腺自身抗体（Tg - Ab 及 TPO - Ab）升高率、术前甲状腺癌诊断率高于对照组（P <0.05）。两组在术前超声检查漏诊率、术中冰冻确诊率、中央区淋巴结转移率、颈侧区淋巴结转移率、肿瘤病灶多发率、甲状腺被膜侵犯率、术后常见并发症发生率、随访期内复发率等方面无显著性差异（P >0.05）。多因素分析显示合并桥本氏甲状腺炎并非甲状腺乳头状癌中央区淋巴结转移的独立风险预测因素（OR =1.286,P >0.05）。结论：甲状腺乳头状癌并发桥本氏甲状腺炎好发于女性,血清甲状腺自身抗体检查有助于桥本氏甲状腺炎术前诊断。并发桥本氏甲状腺炎并不增加甲状腺乳头状癌的术前及术中诊断难度,对甲状腺乳头状癌的临床病理特点也无明显影响。并发桥本氏甲状腺炎的甲状腺乳头状癌可按常规甲状腺癌诊治规范进行治疗。     

Diagnostic usefulness of PCR profiling of the differentially expressed marker genes in thyroid papillary carcinomas

The study was set out to determine whether characteristic changes in the gene expression profile in papillary thyroid carcinoma (PTC) discovered by microarray assays can be used for conventional molecular diagnosis. Expression levels of five reported to be overexpressed and three underexpressed genes were examined in PTC and normal human tissues by real-time PCR and semi-quantitative duplex PCR. Stepwise logistic regression analysis, duplex PCR data evaluation with recursive partition machine algorithm and hierarchical cluster analysis identified SFTPB (upregulated) and TFF3 (downregulated) gene combination as most favorable for differential molecular diagnosis of PTC. Sensitivity, specificity and accuracy obtained in a series of histologically characterized thyroid tumor and normal tissue samples were 88.9, 96.7 and 94.9%, respectively. Applicability of the method to fine needle aspiration biopsy (FNAB) samples was demonstrated using a collection of needle washouts. In spite individual thyroid tumor and normal tissues as well as FNAB samples displayed a substantial degree of variability in the expression levels of analyzed genes, simultaneous molecular analysis of a panel of optimal markers allows making a high probability predictive estimate and may be considered as an informative method of preoperative PTC diagnosis.