RET 和 RAS 突变的预后重要性及其与甲状腺髓样癌 (MTC) 临床病理参数和结果的关系需要澄清。利用 290 名 MTC 患者的数据进行了一项多中心回顾性队列研究。确定分子谱并检查与临床病理数据和结果的关联。在 40 名患者 (16.3%) 中检测到 RET 种系突变。体细胞 RET 和 RAS 突变分别发生在 135 名 (46.9%) 和 57 名 (19.8%) 患者中。 RETM918T 是最常见的体细胞 RET 突变 (n=75)。 RET 体细胞突变与男性、较大的肿瘤大小、晚期 AJCC 分期、血管侵犯 (VI) 和高 IMTCGS 分级相关。与其他 RET 体细胞突变相比，RETM918T 与年轻、AJCC（第 8 版）IV、血管侵犯、甲状腺外扩展和阳性切缘相关。在单变量分析中，RET 体细胞或种系突变与远处无转移生存率降低显着相关，但在调整肿瘤分级和分期后，在多变量分析中没有显着的独立关联。 RET 体细胞突变和 RET 种系突变之间，或者 RETM918T 和其​​他 RET 突变之间的结果没有显着差异。其他复发性分子改变包括 TP53 (4.2%)、ARID2 (2.9%)、SETD2 (2.9%)、KMT2A (2.9%) 和 KMT2C (2.9%)。其中，TP53 突变与总体生存率和疾病特异性生存率下降相关，与肿瘤分级和 AJCC 分期无关。RET 体细胞突变与高级别、侵袭性原发肿瘤特征相关，并降低无远处转移生存率，但这种关系是考虑到肿瘤分级和疾病阶段后并不显着。 RETM918T 与侵袭性原发肿瘤相关，但与临床结果不独立相关。 TP53 突变可能代表与 MTC 总体生存率和疾病特异性生存率下降相关的不良分子事件，但其预后价值需要在未来的研究中得到证实。

The prognostic importance of RET and RAS mutations and their relationship to clinicopathologic parameters and outcomes in medullary thyroid carcinoma (MTC) needs to be clarified.A multicenter retrospective cohort study was performed utilizing data from 290 patients with MTC. The molecular profile was determined and associations were examined with clinicopathologic data and outcomes.RET germline mutations were detected in 40 patients (16.3%). Somatic RET and RAS mutations occurred in 135 (46.9%) and 57 (19.8%) patients respectively. RETM918T was the most common somatic RET mutation (n=75). RET somatic mutations were associated with male sex, larger tumor size, advanced AJCC stage, vascular invasion (VI), and high IMTCGS grade. When compared with other RET somatic mutations, RETM918T was associated with younger age, AJCC (8th edition) IV, vascular invasion, extrathyroidal extension, and positive margins. RET somatic or germline mutations were significantly associated with reduced distant metastasis free survival on univariate analysis but there were no significant independent associations on multivariable analysis, after adjusting for tumor grade and stage. There were no significant differences in outcomes between RET somatic and RET germline mutations, or between RETM918T and other RET mutations. Other recurrent molecular alterations included TP53 (4.2%), ARID2 (2.9%), SETD2 (2.9%), KMT2A (2.9%), and KMT2C (2.9%). Among them, TP53 mutations were associated with decreased overall and disease-specific survival, independently of tumor grade and AJCC stage.RET somatic mutations were associated with high-grade, aggressive primary tumor characteristics, and decreased distant metastatic-free survival but this relationship was not significant after accounting for tumor grade and disease stage . RETM918T was associated with aggressive primary tumors but was not independently associated with clinical outcomes. TP53 mutation may represent an adverse molecular event associated with decreased overall and disease-specific survival in MTC but its prognostic value needs to be confirmed in future studies.