散发性甲状腺髓样癌(sMTC)的临床行为的显着差异导致计划这些患者的治疗时存在不确定性。已经描述了几种肿瘤遗传和表观遗传标记,但其临床用途尚不清楚.这篇综述的目的是评估在sMTC的风险分层和管理中使用分子遗传和表观遗传谱的证据。
使用MeSH术语“髓样癌”搜索MEDLINE和Embase数据库,“表观遗传学”,“分子遗传学”,“microRNAs”;和自由文本术语“髓样癌”,“散发性甲状腺髓样癌”,\"sMTC\",\"RET\",“RAS”和“miR”。包含少于十个主题的文章,不专注于sMTC,排除或未报告临床结局.使用改良版本的纽卡斯尔-渥太华量表评估偏倚风险。
23项研究符合纳入标准,并根据所研究的遗传和表观遗传标记在主题中总结了关键发现。有很好的证据表明,体细胞RET突变预测淋巴结转移和持续性疾病的发生率更高,更糟糕的生存。还有一些高质量的研究表明某些表观遗传标记如肿瘤miR-183和miR-375表达与更高的淋巴结和远处转移率之间的关联。更糟糕的生存。
越来越多的证据表明,肿瘤遗传和表观遗传谱可用于对sMTC患者进行风险分层。进一步的研究应该集中在这些发现的临床适用性上,通过调查针对个体肿瘤突变谱定制管理的可能性。
The significant variation in the clinical behaviour of sporadic
medullary thyroid carcinoma (sMTC) causes uncertainty when planning the management of these patients. Several tumour genetic and epigenetic markers have been described, but their clinical usefulness remains unclear. The aim of this
review was to evaluate the evidence for the use of molecular genetic and epigenetic profiles in the risk stratification and management of sMTC.
MEDLINE and Embase databases were searched using the MeSH terms \"
medullary carcinoma\", \"epigenetics\", \"molecular genetics\", \"microRNAs\"; and free text terms \"
medullary carcinoma\", \"sporadic
medullary thyroid cancer\", \"sMTC\", \"RET\", \"RAS\" and \"miR\". Articles containing less than ten subjects, not focussing on sMTC, or not reporting clinical outcomes were excluded. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale.
Twenty-three studies met the inclusion criteria, and key findings were summarized in themes according to the genetic and epigenetic markers studied. There is good evidence that somatic RET mutations predict higher rates of lymph node metastasis and persistent disease, and worse survival. There are also several good quality studies demonstrating associations between certain epigenetic markers such as tumour miR-183 and miR-375 expression and higher rates of lymph node and distant metastasis, and worse survival.
There is a growing body of evidence that tumour genetic and epigenetic profiles can be used to risk stratify patients with sMTC. Further research should focus on the clinical applicability of these findings by investigating the possibility of tailoring management to an individual\'s tumour mutation profile.