基于分子生物学的甲状腺癌诊疗进展

摘要/Abstract

摘要： 本世纪以来对甲状腺癌的相关分子生物学的研究有了很大的进展。新的分子标记物有助于甲状腺癌诊断以及甲状腺癌预后的评估，通过对这些分子标志物的进一步认识从而指导甲状腺癌手术治疗、术后治疗等个体化策略。也为难治性甲状腺癌治疗带来了新的希望。本文针对甲状腺癌基于分子生物学诊疗策略进行综述。

关键词: 甲状腺癌, 分子标记物, BRAF, 靶向治疗, 进展

Abstract: The reseach on molecular biology of thyroid cancer has made substantial progress since the bigining of this century.New molecular markers emerged helps to improve diagnosis.Further understanding of the molecular markers to help the treatment of thyroid operation,postoperate treatment.Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid caners.In this paper we discuss the molecular-based treatment strategies for thyroid cancer.

Key words: thyroid cancer, molecular markers, BRAF, molecular-targeted treatments, progress

沈雷曹慧敏李苑梁春立. 基于分子生物学的甲状腺癌诊疗进展[J]. 外科研究与新技术, 2015, 4(3): 196-200.

参考文献

[ ] Fugazzola L, De Leo S, Perrino M.The optimal range of RET mutations to be tested: European comments to the guidelines of theAmerican Thyroid Association[J].Thyroid Res, 2013,
6(1):47-51.
[ ] Cataiano MG, Fortunati N, BoccuZZi G. Epigenetics modifications and therapeutic prospects in human thyroid cancer[J].Front Endocrinoi(Lausanne), 2012, 3(40):1-8.
[ ] Xing M. Molecular pathogenesis and mechanisms of thyroid cancer[J]. Nat Rev Cancer. 2013, 13(3): 184-199.
[ ] Wang CC, Friedman L, Kennedy GC, et al. A large multicenter correlation study of thyroid nodule cytopathology and histopathology[J]. Thyroid ,2011, 21(3): 243-251.
[ ] Hou P, Liu D, Shan Y, et al. Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer[J]. Clin Cancer Res, 2007,13: 1161-70.
[ ] Murugan AK, Xing M. Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene[J]. Cancer Res,2011,71: 4403-11.
[ ] Davies H，B‘gneIJ GR，cox c，et al．MuLations of the BRAF gene in human cancer[J]．Nature, 2002,417(6892)：949-954．
[ ]Lim JY, Hong SW, Lee YS, et al. Clinicopathologic implications of the BRAFV600E mutation in papillary thyroid cancer;a subgroup analysis of 3130 cases in a single center [J].Thyorid, 2013, 23 (11): 1423 -30.
[ ] Dujardin F, Pages JC, Collin C et al．BRAF V600E mutation in papillary thyroid carcinoma：prevalence and detection in fine needie aspiration specimem[J]．Ann Pathol, 2010, 30(4)：252-262．
[ ] Xing M, Alzahrani AS, Carson KA, et al.Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer[J]. JAMA, 2013, 309 ( 14 ):1493-1501.
[ ] Elisei R, Viola D, Torregrossa L, et al. The BRAFV600E mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma:single-institution results from a large cohort study[J].J Clin Endocrinol Metab ,2012, 97(12): 4390–98.
[ ]Huang FJ, Fang WY, Ye L,et al. BRAF mutation correlates with recurrent papillary
thyroid carcinoma in Chinese patients[J].Curr Oncol,2014,21(6):740-747.
[ ]Jung YY, Yoo JH, Park ES,et al.Clinicopathologic correlations of the BRAF(V600E) mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma[J].Pathol Res Pract, 2015,211(2):162-170.
[ ] McLeod DSA, Sawka AM, Cooper DS. Controversies in primary treatment of low-risk papillary thyroid cancer[J]. Lancet, 2013, 381:1046–1057.
[ ] So Y K，Son Y I，Park J Y，et al.Preoperative BRAF mutation has different predictive values for lymph node metastasis according to tumor size[J].Otolaryngol Head Neck Surg，2011，145（64）：422-427.
[ ] Yip L, Nikiforova MN, Carty SE, et al. Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation[J]. Surgery ,2009, 146: 1215-23.
[ ] Xing M, Tufano RP, Tufaro AP, et al. Detection of BRAF mutation on fi ne needle aspiration biopsy specimens: a new diagnostic tool for papillary thyroid cancer[J]. J Clin Endocrinol Metab ,2004,89: 2867–2872.
[ ] O’Neill CJ, Bullock M, Chou A, et al. BRAF(V600E) mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer[J]. Surgery,2010, 148(6): 1139–45.
[ ] Barollo S, Pennelli G, Vianello F, et al. BRAF in primary and recurrent papillary thyroid cancers: the relationship with (131)I and2-[(18)F]fl uoro-2-deoxy-D-glucose uptake ability[J]. Eur J Endocrinol,2010,163(4): 659–663.
[ ] Tufano RP, Bishop J, Wu G. Reoperative central compartment dissection for patients with recurrent/persistent papillary thyroid cancer: effi cacy, safety, and the association of the BRAF mutation[J].Laryngoscope, 2012, 122: 1634–40.
[ ] Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications[J]. Endocr Rev ,2007,28(7): 742–62.
[ ] HowelI GM，Carty SE，Armstrong MJ，et aI．Both BRAF V600E mutation and older age(≥65 years) are associated with recrurent papillary thyroid cancer[J]．Ann surg Oncol,2011,18(13)：3566-71．
[ ] Chakravarty D, Santos E, Ryder M, et al. Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation[J]. J Clin Invest ,2011,
121(12): 4700–11.
[ ] Fukahori M, Yoshida A, Hayashi H, et al. The association between RAS gene mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort[J]. Thyroid ,2012,22(7): 683–89.
[ ] Xing M.Molecular pathogenesis and mechanisms of thyroid cancer[J].Nat Rev Cancer,2013,13(3):184-199.
[ ] Lyra J,Vinagre J, Batista R,et al. mTOR activation in medullary thyroid carcinoma with RAS mutation[J].Eur J Endocrinol, 2014,171(5):633-640.
[ ] Rossi M1, Buratto M, Tagliati F, Rossi R, Lupo S, Trasforini G, Lanza G, Franceschetti P, Bruni S, Degli Uberti E, Zatelli MC. Relevance of BRAF(V600E) Mutation Testing Versus RAS Point Mutations and RET/PTC Rearrangements Evaluation in the Diagnosis of Thyroid Cancer[J]. Thyroid,2015;25(2):221-228.
[ ] Ersoz S, Sert H, Yandi M, et a1．The significance of galectin-3 expression in the immunocytochemical evaluafion of thyroid fine needle aspiration cytology[J]．Pathol Oncol Res,2008，14(4)：457-460．
[ ] Lin CI, Whang EE, Donner DB, et al．Galectin-3 targeted therapy with a small molecule inhibitor activates apoptosis and enhances both chemosensitivity and radiosensitivity in papillary thyroid cincer[J]．Mol Cancer Res,2009,7(10)：1655-1662．
[ ]Pillai S, Gopalan V , Smith RA , et al.Diffuse sclerosing variant of papillary thyroid carcinoma-an update of its clinicopathological features and molecular biology. Crit Rev Oncol Hematol[J]. 2014，12（4）：104-108.
[ ] Herrmann BL, Schmid KW, Goerges R, et a1. Calcitonin screening and pentagastrin testing:predictive value for the diagnosis of medullarycarcinoma in nodular thyroid disease[J]．Eur J Endocrinol, 2010,162(6)：1141-45．
[ ] Meijer JA，Le Cessie S，Van den Hout WB, et a1．Calcitonin and carcinoembryonic antigen doubling times asprognostic factors inmedullary thyroid carcinoma：a stuctured meta-analysis[J]．Clin Endocrinol,2010,72(4)：534-542．
[ ] Torregrossa L，Faviana P, Filice ME，et a1．CXC Chemokine receptor 4 immunodetection in the follicular variant of papillary thyroid carcinoma：comparison to galectin-3 and hector battifora mesothelial cell[J]．Thyroid，2010, 20(5)：495-504．
[ ] Wallander M，fLayfield LJ，Jarboe E，et a1．Follicular variant of papillary carcinoma：reproducibility of histologic diagnosis and utility of HBME-1 immunohistochemistry and BRAF mutational analysis as diagnostic adjuncts[J]．Appl Immunohistochem Mol Morphol
,2010，18(3)：231-235．
[ ] Xiong-Wei Huo，Yan-Feng Gao，Qing-Yong Ma, et a1．The expression and significance of hTERT and P53 in thyroid carcinoma[J]．Academic Journal of xi’an Jiao Tong University(English
Edition)，2010, 22(2)：127-130．
[ ] Algeciras-Schinmich A, Milosevic D，Mclver B, et a1．Evaluation of the PAX8／PPARG tanslocation in follicular thyroid cancer with a 4-color reverse-transcription PCR assay and automated high-resolution fragment analysis[J]．Clin Chem, 2010, 56(3)：391-398．
[ ] Pallante P, Visone R, Croce CM, et a1．Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas[J]．Endocr Relat Cancer, 2010, 17(1)：91-104．
[ ] Pennelli G, Galuppini F, Barollo S,et al. The PDCD4/miR-21 pathway in medullary
thyroid carcinoma[J].Hum Pathol.2015 ;46(1):50-7.
[ ] Hamatani K, Eguchi H, Ito R, et a1．RET／PTC rearrangements preferentially occurred in papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose[J]．Cancer Res, 2008, 68(17):7 176-82．
[ ] Lin CI,Whang EE, Abramson MA，et a1．Galectin-3 regulates apoptosis and doxorubicin chemoresistance in papillary thyroid cancer cells[J]．Biochem Biophys Res Commun, 2009, 379(2)：626-631．

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