摘要
桥本氏甲状腺炎(HT)与甲状腺乳头状癌(PTC)的相关性以及HT是否会促进PTC的发生发展多年来是一个有争议的话题,近年来大量研究证实HT与PTC的发生发展有着密切的关系。肿瘤的产生可以认为是肿瘤细胞本身异常的生理特性、肿瘤微环境的形成及外部环境因素影响共同作用的结果。HT被认为是一种慢性炎症反应,浸润在HT患者甲状腺周围的各种炎性细胞会损伤间质细胞的DNA,导致DNA的错误修复,从而促进PTC的发生。肿瘤微环境通过影响免疫监视与肿瘤扩散在肿瘤发生和发展的不同阶段发挥关键作用。PTC相关巨噬细胞和肥大细胞产生的趋化因子可诱导产生大量免疫细胞,浸润性免疫细胞和PTC细胞之间复杂的相互作用已经成为影响PTC发生发展的重要因素。在分子机制方面,HT促进PTC发生发展与RET基因的重排、p63蛋白质的表达、RAS、BRAF基因的突变和PI3K/Akt的表达相关。在免疫机制研究中,发现CD3+,CD4+和Th17细胞在PTC的发生发展中起到重要的作用。内分泌方面,长期HT引起促甲状腺激素(TSH)升高也是PTC发生发展以及术后复发的独立危险因素。在临床大数据方面,HT是PTC发生的独立危险因素,患有HT的患者中PTC的发病率明显升高。同时PTC的患者中HT的患病率也明显高于不患有PTC患者的患病率。石蜡病理中发现合并了HT的PTC结节比单纯的PTC结节具有更好的临床病理特征以及预后。PTC合并HT的患者恶性结节多灶性发生率更高,但PTC合并HT的恶性结节中央区淋巴结转移率更低、结节直径更小、远处转移发生率也更低。在这些患者的PTC结节中BRAF^(V600E)基因突变率更低,这说明HT对于PTC患者预后的良好保护作用。HT和PTC的相关性是目前甲状腺方面的研究热点,近几年很多学者在分子机制方面做了大量的研究。相关的临床特征可以进一步指导临床医生对于PTC患者临床特征和预后的判断。充分认识HT和PTC的相关性将有助于加深对PTC发生机制的理解,可为PTC的免疫治疗提供新的思路和方法。
The association between Hashimoto's thyroiditis(HT)and papillary thyroid carcinoma(PTC)and whether HT can promote the occurrence and development of PTC have been a controversial topic for many years.In recent years,many studies have confirmed that there is a close relationship between HT and the occurrence and development of PTC.Tumorigenesis can be regarded as the joint outcome of the abnormal features of tumor cells,the influences of the formation of tumor microenvironment and external environmental factors.HT is considered as a chronic inflammatory reaction,and various inflammatory cells infiltrating around the thyroid gland of HT patients will damage the DNA of interstitial cells,leading to the wrong repair of DNA,thus promoting the occurrence of PTC.Tumor microenvironment plays a key role in different stages of tumorigenesis and development of tumors by affecting immune surveillance and tumor diffusion.Chemokines produced by PTC-associated macrophages and mast leukocytes can induce the production of various immune cells.The complex interaction between infiltrating immune cells and PTC cells has become an important factor affecting the occurrence and development of PTC.In terms of molecular mechanism,HT promoting the occurrence and development of PTC is related to RET gene rearrangement,p63 protein expression,RAS,BRAF gene mutation and PI3K/Akt expression.In the aspect of immune mechanism,CD3+,CD4+and Th17 cells were found to play important roles in the occurrence and development of PTC.As for the endocrine aspect,the increase of thyroid-stimulating hormone(TSH)caused by long-term HT is also an independent risk factor for the occurrence,development,and postoperative recurrence of PTC.As regards to the big clinical data,HT is an independent risk factor for PTC,and the incidence rate of PTC was significantly higher in patients with HT.At the same time,the prevalence of HT in patients with PTC was significantly higher than that in patients without PTC.Paraffin pathology found that patients with PTC nodules and concomitant HT had better clinicopathologic features and prognosis than those with lone PTC nodules.The patients with PTC and HT had a higher incidence of multifocality of malignant nodules,but the patients with PTC and HT had a lower incidence of central lymph node metastasis,smaller nodule diameter and lower incidence of distant metastasis.The mutation rate of BRAF^(V600E) gene was lower in PTC nodules of these patients,which indicate that HT have a good protective effect on the prognosis of PTC patients.The correlation between HT and PTC is a hot topic in thyroid research.In recent years,many scholars have conducted a lot of studies on the molecular mechanism.Relevant clinical features can further guide clinicians to judge the clinical characteristics and prognosis of PTC patients.Fully understanding the correlation between HT and PTC will help to deepen the understanding of the pathogenesis of PTC and provide new ideas and methods for immunotherapy of PTC.
作者
粟敦涛
欧阳辉
李新营
SU Duntao;OUYANG hui;LI Xinying(Department of Thyroid Surgery,Xiangya Hospital,Central South University,Changsha 410008,China)
出处
《中国普通外科杂志》
CAS
CSCD
北大核心
2021年第5期606-612,共7页
China Journal of General Surgery
基金
国家自然科学基金资助项目(82073262)。
关键词
甲状腺癌
乳头状
桥本病
综述
Thyroid Cancer
Papillary
Hashimoto Disease
Review
