A Shift in Molecular Drivers of Papillary Thyroid Carcinoma Following the 2017 World Health Organization Classification: Characterization of 554 Consecutive Tumors With Emphasis on BRAF-Negative Cases

被引:10
作者
Hang, Jen-Fan [1 ,2 ,3 ]
Chen, Jui-Yu [2 ,4 ,5 ]
Kuo, Po-Chung [2 ,4 ]
Lai, Hon-Fan [2 ,4 ]
Lee, Tsung-Lun [2 ,6 ]
Tai, Shyh-Kuan [2 ,6 ]
Kuo, Chin-Sung [2 ,7 ]
Chen, Harn-Shen [2 ,7 ]
Li, Wan-Shan [8 ,9 ]
Li, Chien-Feng [10 ,11 ]
机构
[1] Taipei Vet Gen Hosp, Dept Pathol & Lab Med, Taipei, Taiwan
[2] Natl Yang Ming Chiao Tung Univ, Sch Med, Taipei, Taiwan
[3] Natl Yang Ming Chiao Tung Univ, Inst Clin Med, Taipei, Taiwan
[4] Taipei Vet Gen Hosp, Dept Surg, Div Gen Surg, Taipei, Taiwan
[5] Natl Def Med Ctr, Inst Biol & Anat, Taipei, Taiwan
[6] Taipei Vet Gen Hosp, Dept Otolaryngol, Taipei, Taiwan
[7] Taipei Vet Gen Hosp, Div Endocrinol & Metab, Dept Med, Taipei, Taiwan
[8] Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan
[9] Chung Hwa Univ Med Technol, Dept Med Technol, Tainan, Taiwan
[10] Chi Mei Med Ctr, Dept Med Res, Tainan, Taiwan
[11] Natl Hlth Res Inst, Natl Inst Canc Res, Tainan, Taiwan
关键词
ALK; BRAF; NTRK; papillary thyroid carcinoma; RAS; RET; FOLLICULAR VARIANT; V600E MUTATION; CANCER; ASSOCIATION; EFFICACY; ALK;
D O I
10.1016/j.modpat.2023.100242
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Most studies for comprehensive molecular profiling of papillary thyroid carcinoma (PTC) have been performed before the 2017 World Health Organization (WHO) classification, in which the diagnostic criteria of follicular variants of PTC have been modified and noninvasive follicular thyroid neoplasm with papillary-like nuclear features has been introduced. This study aims to investigate the shift in the incidence of BRAF V600E mutations in PTCs following the 2017 WHO classification and to further characterize the histologic subtypes and molecular drivers in BRAF-negative cases. The study cohort consisted of 554 consecutive PTCs larger than 0.5 cm between January 2019 and May 2022. Immunohistochemistry for BRAF VE1 was performed for all cases. Compared with a historical cohort of 509 PTCs from November 2013 to April 2018, the incidence of BRAF V600E mutations was significantly higher in the study cohort (86.8% vs 78.8%, P 1/4 .0006). Targeted RNA-based next-generation sequencing using a FusionPlex Pan Solid Tumor v2 panel (ArcherDX) was performed for BRAF-negative PTCs from the study cohort. Eight cribriform-morular thyroid carcinomas and 3 cases with suboptimal RNA quality were excluded from next-generation sequencing. A total of 62 BRAF-negative PTCs were successfully sequenced, including 19 classic follicular predominant PTCs, 16 classic PTCs, 14 infiltrative follicular PTCs, 7 encapsulated follicular PTCs, 3 diffuse sclerosing PTCs, 1 tall cell PTC, 1 solid PTC, and 1 diffuse follicular PTC. Among them, RET fusions were identified in 25 cases, NTRK3 fusions in 13 cases, BRAF fusions in 5 cases including a novel TNS1::BRAF fusion, NRAS Q61R mutations in 3 cases, KRAS Q61K mutations in 2 cases, NTRK1 fusions in 2 cases, an ALK fusion in 1 case, an FGFR1 fusion in 1 case, and an HRAS Q61R mutation in 1 case. No genetic variants, from our commercially employed assay, were detected in the remaining 9 cases. In summary, the incidence of BRAF V600E mutations in PTCs significantly increased from 78.8% to 86.8% in our poste2017 WHO classification cohort. RAS mutations accounted for only 1.1% of the cases. Driver gene fusions were identified in 8.5% of PTCs and were clinically relevant given the emerging targeted kinase inhibitor therapy. Of the 1.6% of cases for which no driver alteration was detected, the specificity of drivers tested and tumor classification require further investigation.& COPY; 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.
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页数:10
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共 41 条
  • [1] Integrated Genomic Characterization of Papillary Thyroid Carcinoma
    Agrawal, Nishant
    Akbani, Rehan
    Aksoy, B. Arman
    Ally, Adrian
    Arachchi, Harindra
    Asa, Sylvia L.
    Auman, J. Todd
    Balasundaram, Miruna
    Balu, Saianand
    Baylin, Stephen B.
    Behera, Madhusmita
    Bernard, Brady
    Beroukhim, Rameen
    Bishop, Justin A.
    Black, Aaron D.
    Bodenheimer, Tom
    Boice, Lori
    Bootwalla, Moiz S.
    Bowen, Jay
    Bowlby, Reanne
    Bristow, Christopher A.
    Brookens, Robin
    Brooks, Denise
    Bryant, Robert
    Buda, Elizabeth
    Butterfield, Yaron S. N.
    Carling, Tobias
    Carlsen, Rebecca
    Carter, Scott L.
    Carty, Sally E.
    Chan, Timothy A.
    Chen, Amy Y.
    Cherniack, Andrew D.
    Cheung, Dorothy
    Chin, Lynda
    Cho, Juok
    Chu, Andy
    Chuah, Eric
    Cibulskis, Kristian
    Ciriello, Giovanni
    Clarke, Amanda
    Clayman, Gary L.
    Cope, Leslie
    Copland, John A.
    Covington, Kyle
    Danilova, Ludmila
    Davidsen, Tanja
    Demchok, John A.
    DiCara, Daniel
    Dhalla, Noreen
    [J]. CELL, 2014, 159 (03) : 676 - 690
  • [2] High Prevalence of DICER1 Mutations and Low Frequency of Gene Fusions in Pediatric Follicular-Patterned Tumors of the Thyroid
    Bae, Ja-Seong
    Jung, Seung-Hyun
    Hirokawa, Mitsuyoshi
    Bychkov, Andrey
    Miyauchi, Akira
    Lee, Sohee
    Chung, Yeun-Jun
    Jung, Chan Kwon
    [J]. ENDOCRINE PATHOLOGY, 2021, 32 (03) : 336 - 346
  • [3] Recurrent uterine inflammatory myofibroblastic tumor previously managed as leiomyosarcoma has sustained response to alectinib
    Carballo, Erica V.
    Pham, Tra V.
    Turashvili, Gulisa
    Hanley, Krisztina
    Starbuck, Kristen D.
    Meisel, Jane L.
    [J]. GYNECOLOGIC ONCOLOGY REPORTS, 2022, 43
  • [4] Trends in thyroid cancer burden in Taiwan over two decades
    Cheng, Sheena Yi-Hsin
    Hsu, Yi-Chiung
    Cheng, Shih-Ping
    [J]. CANCER CAUSES & CONTROL, 2023, 34 (06) : 553 - 561
  • [5] Chu Ying-Hsia, 2023, Surg Pathol Clin, V16, P57, DOI 10.1016/j.path.2022.09.007
  • [6] Clinicopathologic features of kinase fusion-related thyroid carcinomas: an integrative analysis with molecular characterization
    Chu, Ying-Hsia
    Wirth, Lori J.
    Farahani, Alexander A.
    Nose, Vania
    Faquin, William C.
    Dias-Santagata, Dora
    Sadow, Peter M.
    [J]. MODERN PATHOLOGY, 2020, 33 (12) : 2458 - 2472
  • [7] Clinicopathologic and molecular characterization ofNTRK-rearranged thyroid carcinoma (NRTC)
    Chu, Ying-Hsia
    Dias-Santagata, Dora
    Farahani, Alexander A.
    Boyraz, Baris
    Faquin, William C.
    Nose, Vania
    Sadow, Peter M.
    [J]. MODERN PATHOLOGY, 2020, 33 (11) : 2186 - 2197
  • [8] Uterine Inflammatory Myofibroblastic Neoplasms With Aggressive Behavior, Including an Epithelioid Inflammatory Myofibroblastic Sarcoma A Clinicopathologic Study of 9 Cases
    Collins, Katrina
    Ramalingam, Preetha
    Euscher, Elizabeth D.
    Reques Llanos, Armando
    Garcia, Angel
    Malpica, Anais
    [J]. AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2022, 46 (01) : 105 - 117
  • [9] Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Patients With NTRK Fusion-Positive Solid Tumors
    Demetri, George D.
    De Braud, Filippo
    Drilon, Alexander
    Siena, Salvatore
    Patel, Manish R.
    Cho, Byoung Chul
    Liu, Stephen, V
    Ahn, Myung-Ju
    Chiu, Chao-Hua
    Lin, Jessica J.
    Goto, Koichi
    Lee, Jeeyun
    Bazhenova, Lyudmila
    John, Thomas
    Fakih, Marwan
    Chawla, Sant P.
    Dziadziuszko, Rafal
    Seto, Takashi
    Heinzmann, Sebastian
    Pitcher, Bethany
    Chen, David
    Wilson, Timothy R.
    Rolfo, Christian
    [J]. CLINICAL CANCER RESEARCH, 2022, 28 (07) : 1302 - 1312
  • [10] Clinicopathological features and outcomes of thyroid nodules with EIF1AX mutations
    French, Esra Karslioglu
    Nikitski, Alyaksandr, V
    Yip, Linwah
    Nikiforova, Marina N.
    Nikiforov, Yuri E.
    Carty, Sally E.
    [J]. ENDOCRINE-RELATED CANCER, 2022, 29 (08) : 467 - 473