Fussey Jonathan Mark, Vaidya Bijay, Kim Dae, Clark Jonathan, Ellard Sian, Smith Joel Anthony
Department of Head and Neck Surgery, Royal Devon and Exeter Hospital, Exeter, UK.
Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter, Exeter, UK.
Clin Endocrinol (Oxf). 2019 Dec;91(6):697-707. doi: 10.1111/cen.14060. Epub 2019 Jul 29.
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.
散发性甲状腺髓样癌（sMTC）临床行为的显著差异使得在规划这些患者的治疗方案时存在不确定性。已经描述了几种肿瘤遗传和表观遗传标志物，但其临床实用性仍不明确。本综述的目的是评估分子遗传和表观遗传谱在sMTC风险分层和治疗中的应用证据。
使用医学主题词“髓样癌”、“表观遗传学”、“分子遗传学”、“微小RNA”在MEDLINE和Embase数据库中进行检索；并使用自由文本词“髓样癌”、“散发性甲状腺髓样癌”、“sMTC”、“RET”、“RAS”和“miR”。排除受试者少于10例、未聚焦于sMTC或未报告临床结果的文章。使用改良版的纽卡斯尔-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志物将主要发现归纳为不同主题。有充分证据表明，体细胞RET突变预示着更高的淋巴结转移率和疾病持续率，以及更差的生存率。也有几项高质量研究表明，某些表观遗传标志物如肿瘤miR-183和miR-375表达与更高的淋巴结和远处转移率以及更差的生存率之间存在关联。
越来越多的证据表明，肿瘤遗传和表观遗传谱可用于sMTC患者的风险分层。进一步的研究应通过调查根据个体肿瘤突变谱定制治疗方案的可能性，聚焦于这些发现的临床适用性。
