散发性甲状腺髓样癌病理分级标准的预后评估价值及全外显子测序分析

Sporadic medullary thyroid carcinoma:prognostic value of pathological grading and whole exome sequencing analysis

目的探讨散发性甲状腺髓样癌(medullary thyroid carcinoma,MTC)的临床病理特征及分子机制,探索潜在的治疗靶点。方法收集2010年1月至2022年12月手术切除并且根据家族史及个人疾病史筛选的32例散发性MTC患者,分析其临床特征、病理分级、免疫组织化学表达。对6例散发性MTC石蜡包埋标本行全外显子测序分析。结果相比于病理分级为低级别的散发性MTC,高级别的散发性MTC与未能达到生化治愈和发生淋巴结转移有关(χ^(2)=4.428,P=0.040;χ^(2)=4.072,P=0.044)。病理分级、生化治愈、TNM分期是患者无病生存期的独立预后因素(均P<0.05)。6例散发性MTC肿瘤及其配对正常组织全外显子测序结果表明,RET、RAS基因是主要驱动突变(比例均为3/6),RET、RAS基因突变的患者均无复发,此外还检测到1例PDGFRA基因突变。结论病理分级系统对散发性MTC具有重要的预后预测价值。RET和RAS基因突变是散发性MTC主要驱动突变,PDGFRA基因是散发性MTC潜在的治疗靶点。

ObjectiveTo explore the clinicopathological and genetic characteristics of sporadic medullary thyroid carcinoma(MTC)and new therapeutic targets for sporadic MTC.MethodsBased on family and personal disease history,we identified 32 sporadic MTC who underwent surgical resection from Jan 2010 to Dec 2022.Clinicopathological and immunohistochemical features were analyzed in all patients,while 6 of them were subject to the whole exome sequencing(WES).ResultsCompared with those of low-grade sporadic MTC,patients with high-grade tumors were more likely to have lymph node metastasis at presentation(χ^(2)=4.428,P=0.040);less likely to be cured by biochemical treatment(χ^(2)=4.072,P=0.044).Pathological grading scheme,biochemical cure,and TNM stage were independent risk factors of disease free survival.WES was performed on 6 pairs of normal tissues.We screened RET and RAS as driver mutations,and the mutation ratio was 3/6 respectively.Patients with RET or RAS mutations had no recurrence.In addition,we detected PDGFRA somatic mutation,with a mutation ratio of 1/6.ConclusionsFor sporadic MTC cases,the pathological grading system has important prognostic value,and RET and RAS somatic mutations are the main driver mutations.PDGFRA are potential therapeutic targets for sporadic MTC.