Table_1_TERT Promoter Mutations Are an Independent Predictor of Distant Metastasis in Middle Eastern Papillary Thyroid Microcarcinoma.docx

BackgroundPapillary thyroid microcarcinomas (PTMCs) have been attributed to the recent increased incidence of thyroid cancer. Although indolent, a subset of PTMC could potentially develop distant metastasis (DM). This study aimed to evaluate the clinico-pathological features and molecular characteristics of PTMC and identify the risk factors for DM in PTMC patients from Middle Eastern ethnicity.
MethodsWe retrospectively analyzed 210 patients with histologically confirmed PTMC. Clinico-pathological associations for DM, BRAF mutation and TERT mutation were analyzed successfully in 184 patients. Multivariate analysis was performed using Cox proportional hazards model and logistic regression analysis.
ResultsAmong the PTMC patients included in this cohort, DM was noted in 6.0% (11/184), whereas tumor relapse occurred in 29/184 (15.8%). Of the 11 cases with DM, lung metastasis occurred in 8 cases, bone metastasis in 2 cases and brain metastasis in 1 case. Presence of extrathyroidal extension and male sex were significantly associated with DM. Molecular analysis showed BRAF V600E mutations to be the most frequent, being detected in 45.7% (84/184). TERT promoter mutations were detected in 16 (8.7%) cases and were significantly associated with DM and shorter metastasis-free survival in multivariate analysis.
ConclusionsOur study indicates a surprisingly high frequency of TERT promoter mutation in Saudi patients with PTMC. Identifying TERT promoter mutations as an independent predictor of DM in patients with microcarcinoma could explain the inherent aggressive nature of PTMC from Middle Eastern ethnicity and magnify its role in patient risk stratification, which might help in improving therapeutic strategy for these patients.

研究背景
甲状腺乳头状微小癌（Papillary thyroid microcarcinomas, PTMCs）被认为是近期甲状腺癌发病率升高的重要诱因之一。尽管该肿瘤多呈惰性病程，但部分PTMC患者仍可能发生远处转移（Distant Metastasis, DM）。本研究旨在评估中东血统PTMC患者的临床病理特征与分子生物学特性，并明确其发生远处转移的危险因素。
研究方法
本研究回顾性分析了210例经组织病理学确诊的PTMC患者。最终成功对184例患者的远处转移、BRAF突变及TERT突变相关的临床病理关联进行了分析。采用Cox比例风险模型与logistic回归分析开展多因素统计分析。
研究结果
本队列纳入的PTMC患者中，6.0%（11/184）发生了远处转移，另有15.8%（29/184）的患者出现肿瘤复发。在11例发生远处转移的患者中，8例为肺转移、2例为骨转移、1例为脑转移。甲状腺外侵犯与男性性别与远处转移显著相关。分子生物学分析显示，BRAF V600E突变是最常见的突变类型，检出率为45.7%（84/184）。TERT启动子突变检出率为8.7%（16/184），多因素分析显示该突变与远处转移及更短的无转移生存期显著相关。
研究结论
本研究表明，沙特阿拉伯PTMC患者的TERT启动子突变频率远超预期。明确TERT启动子突变可作为微小癌患者发生远处转移的独立预测因子，有助于解释中东血统PTMC所固有的侵袭性特征，并强化其在患者风险分层中的作用，从而为优化此类患者的治疗策略提供理论依据。