Abstract
Purpose
Locally 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.
Methods
An 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.
Results
This study showed that the main mutation is common BRAFV600E (66.2%, 43/65) in LAPTC, followed by the TERT promoter mutations (38.5%, 25/65). Synergetic mutations of BRAFV600E 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).
Conclusions
Synergetic 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.
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Data availability
Study data will be made available upon request and with appropriate institutional approvals.
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Funding
This work has been supported by National Nature Science Foundation of China (Grant No. 81972500, 81972543), Natural Science Foundation of Shandong Province, China (Grant No. ZR2019MH024), Grant from Innovation Program of Shanghai Science and technology committee (20Z11900304), Grant from Shanghai Clinical research key support project/ Science and Technology commission of Shanghai Municipality (SHDC2020CR6003-002), and Clinical research funds from Shanghai Jiao Tong University Affiliated Sixth People's Hospital (Zhiyan Liu).
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ZD and XT performed the experiments and wrote the paper. XD, BG, JK, BW, ZY, CC, PL and YZ acted as the assistants. YF and ZL were responsible for the design and for funding collection. All authors read and approved the final manuscript.
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This study was approved by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, and all patients provided signed informed consent.
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Ding, Z., Tao, X., Deng, X. et al. Genetic analysis and clinicopathologic features of locally advanced papillary thyroid cancers: a prospective observational study. J Cancer Res Clin Oncol 149, 6303–6313 (2023). https://doi.org/10.1007/s00432-022-04541-w
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DOI: https://doi.org/10.1007/s00432-022-04541-w