Genetic analysis and clinicopathologic features of locally advanced papillary thyroid cancers: a prospective observational study
Genetic analysis and clinicopathologic features of locally advanced papillary thyroid cancers: a prospective observational study
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DOI：
10.1007/s00432-022-04541-w
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发表时间：
2023-02-03
影响因子：
3.6
通讯作者：
Liu, Zhiyan
中科院分区：
文献类型：
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作者：
Ding, Zheng;Tao, Xuanbin;Liu, Zhiyan
目的局部晚期甲状腺乳头状癌（LAPTC）预后差。大规模的基因组测试揭示了多种致癌驱动因素，这可能是了解肿瘤进展所必需的。然而，甲状腺癌高复发风险和预后差的准确识别仍不清楚。本研究的目的是分析局部晚期甲状腺乳头状癌的遗传特征和临床病理特征。MethodsAn观察性队列研究进行，以确定LAPTC的分子特征和不同基因突变的LAPTC的预后比较。在新鲜肿瘤组织上进行ThyroSeq v2下一代测序（57基因组）。比较不同基因突变的肿瘤的临床病理特征。此外，肿瘤复发和无病生存的相关性与不同的遗传alternations.ResultsThis研究表明，主要的突变是常见的BRAF（V600 E）（66.2%，43/65），在LAPTC，其次是TERT启动子突变（38.5%，25/65）。在26.2%（17/65）的LAPTC中鉴定出BRAF（V600 E）和TERT启动子（B&T）的协同突变，其与高细胞变异、甲状腺外浸润和晚期肿瘤分期（III/IV）相关。B&T的协同突变也与较高的复发风险显著相关（风险比[HR]，6.0; 95%置信区间，CI 1.26-28.55，P = 0.02）和死亡率结论B&T协同突变在LAPTC中常见，其与侵袭性临床病理特征以及复发和死亡风险增加相关。这一发现可能有助于预测LAPTC的攻击行为，并协助临床决策。
PurposeLocally advanced papillary thyroid cancer (LAPTC) has poor prognosis. Large-scale genomic testing has revealed multiple oncogenic drivers which may be essential for understanding tumor progression. However, the accurate identification of high recurrence risk and poor prognosis in thyroid carcinoma remains unclear. The objective of this study was to analyze genetic profile and clinicopathologic features of locally advanced papillary thyroid cancers.MethodsAn observational cohort study was performed to identify molecular characteristics of LAPTC and a prognosis comparison of LAPTC with different genetic mutations. ThyroSeq v2 next-generation sequencing (57-gene panel) was performed on fresh tumor tissue. Then, the clinicopathological features between tumors with different genetic mutations were compared. Additionally, correlations of tumor recurrence and disease free survival with different genetic alterations were analyzed.ResultsThis study showed that the main mutation is common BRAF(V600E) (66.2%, 43/65) in LAPTC, followed by the TERT promoter mutations (38.5%, 25/65). Synergetic mutations of BRAF(V600E) and TERT promoters (B&T) were identified in 26.2% LAPTC (17/65), which is associated with tall-cell variant, extrathyroidal invasion and advanced tumor stage (III/IV). The synergetic mutations of B&T are also significantly associated with higher risk of recurrence (hazard ratio [HR], 6.0; 95% confidence interval, CI 1.26-28.55, P = 0.02) and mortality (17.6%, 3/17).ConclusionsSynergetic mutations of B&T are common in LAPTC, which is associated with the aggressive clinicopathologic features and an increased risk of recurrence and mortality. This finding may help to predict aggressive behavior of LAPTC and to assist in clinical decision-making.