Department of Pathology and Laboratory Medicine; New York, New York, USA.
Department of Pathology, Emory University Hospital Midtown, Atlanta, Georgia, USA.
Thyroid. 2024 Feb;34(2):167-176. doi: 10.1089/thy.2023.0279. Epub 2023 Nov 7.
The prognostic importance of and mutations and their relationship to clinicopathologic parameters and outcomes in medullary thyroid carcinoma (MTC) need 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. germ line mutations were detected in 40 patients (16.3%). Somatic and mutations occurred in 135 (46.9%) and 57 (19.8%) patients, respectively. was the most common somatic mutation ( = 75). somatic mutations were associated with male sex, larger tumor size, advanced American Joint Committee Cancer (AJCC) stage, vascular invasion, and high International Medullary Thyroid Carcinoma Grading System (IMTCGS) grade. When compared with other somatic mutations, was associated with younger age, AJCC (eighth edition) IV, vascular invasion, extrathyroidal extension, and positive margins. somatic or germ line 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 somatic and germ line mutations, or between and other mutations. Other recurrent molecular alterations included (4.2%), (2.9%), (2.9%), (2.9%), and (2.9%). Among them, mutations were associated with decreased overall survival (OS) and disease-specific survival (DSS), independently of tumor grade and AJCC stage. 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. was associated with aggressive primary tumors but was not independently associated with clinical outcomes. mutation may represent an adverse molecular event associated with decreased OS and DSS in MTC, but its prognostic value needs to be confirmed in future studies.
需要阐明 和 突变的预后意义及其与甲状腺髓样癌 (MTC) 的临床病理参数和结局的关系。利用来自 290 例 MTC 患者的数据，进行了一项多中心回顾性队列研究。确定了分子谱，并检查了与临床病理数据和结局的关联。在 40 例患者 (16.3%) 中检测到胚系 突变。体细胞 和 突变分别发生在 135 例 (46.9%) 和 57 例 (19.8%) 患者中。 是最常见的体细胞 突变 ( = 75)。体细胞突变与男性、更大的肿瘤大小、更晚期的美国联合委员会癌症 (AJCC) 分期、血管侵犯和更高的国际甲状腺髓样癌分级系统 (IMTCGS) 分级相关。与其他 体细胞突变相比， 与更年轻的年龄、AJCC (第八版) IV 期、血管侵犯、甲状腺外延伸和阳性切缘相关。体细胞或胚系 突变与无远处转移生存的单变量分析显著相关，但多变量分析在调整肿瘤分级和分期后无显著独立相关性。 体细胞或胚系突变之间，或 和其他 突变之间，在结局方面没有显著差异。其他常见的分子改变包括 (4.2%)、 (2.9%)、 (2.9%)、 (2.9%)和 (2.9%)。其中， 突变与总生存 (OS) 和疾病特异性生存 (DSS) 降低相关，与肿瘤分级和 AJCC 分期无关。 体细胞突变与高级别、侵袭性原发性肿瘤特征以及远处无转移生存时间缩短相关，但在考虑到肿瘤分级和疾病分期后，这种关系并不显著。 与侵袭性原发性肿瘤相关，但与临床结局无关。 突变可能代表 MTC 中与 OS 和 DSS 降低相关的不良分子事件，但需要在未来研究中证实其预后价值。
