Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2025 Sep 1;36(1):30.
doi: 10.1007/s12022-025-09875-y.

Progression of Follicular Thyroid Carcinomas to Anaplastic Thyroid Carcinomas: Molecular and Clinicopathologic Characteristics with Comparison to Papillary Thyroid Carcinoma-Derived Anaplastic Thyroid Carcinomas

Toru Odate  1   2 , Tetsuo Kondo  1 , Ryohei Katoh  3 , Koichi Ito  4 , Toshihide Ueno  5 , Yasushi Yatabe  2   6 , Taisuke Mori  7   8
Affiliations
Comparative Study

Progression of Follicular Thyroid Carcinomas to Anaplastic Thyroid Carcinomas: Molecular and Clinicopathologic Characteristics with Comparison to Papillary Thyroid Carcinoma-Derived Anaplastic Thyroid Carcinomas

Toru Odate et al. Endocr Pathol. .

Abstract

Although anaplastic thyroid carcinomas (ATCs) typically arise from papillary thyroid carcinomas (PTCs), follicular thyroid carcinomas (FTCs) can also progress to ATCs; however, histologically confirmed FTC-derived ATCs are relatively uncommon and remain poorly characterized. To clarify this phenomenon, we analyzed eight FTC-derived ATCs and compared them with 11 PTC-derived ATCs. Whole-exome sequencing (WES) was conducted on the differentiated thyroid carcinoma (DTC) and ATC components within the same tumors to examine mutational profiles; three additional cases underwent FoundationOne® testing. The demographic features were similar between FTC- and PTC-derived ATCs. Histologically, spindle-cell morphology was more common in FTC-derived ATCs (3/8), whereas PTC-derived ATCs exhibited squamoid (5/11) and giant cell features (5/11), including osteoclast-like cells. WES was successfully performed on both the ATC and FTC components in seven of the eight FTC-derived ATCs. Common alterations included TERT promoter (5/7), NRAS (4/7), and HRAS (2/7) mutations in both components. TP53 mutations were observed only in the ATC component (5/7). EIF1AX mutations co-occurred with TERT and HRAS mutations in two cases. PTEN mutations were found in two FTCs with solid/trabecular patterns but were absent in the corresponding ATC components. One tumor harbored a DGCR8 p.E518K mutation that was retained during progression. By contrast, PTC-derived ATCs consistently showed concurrent BRAF and TERT promoter mutations (11/11). Immunohistochemistry for BRAF V600E, RAS Q61R, p53, PTEN, and MTAP showed high concordance with the corresponding mutation status. These findings revealed significant histological and genetic differences between FTC- and PTC-derived ATCs, providing new insights into the molecular basis of FTC dedifferentiation into ATC.

Keywords: Anaplastic thyroid carcinoma; Follicular thyroid carcinoma; Mutation; Papillary thyroid carcinoma; Progression.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics Approval: The Institutional Review Boards of the National Cancer Center Hospital (2010–077) and Ito Hospital (471) approved this study. Consent to Participate: Not applicable. Consent for Publication: All authors agree to the publication of this manuscript. Competing interests: The authors have no conflict of interest to declare.

Similar articles

See all similar articles

References

    1. Lin B, Ma H, Ma M, Zhang Z, Sun Z, Hsieh IY, Okenwa O, Guan H, Li J, Lv W (2019) The incidence and survival analysis for anaplastic thyroid cancer: a SEER database analysis. Am J Transl Res 11 (9):5888-5896 - PubMed - PMC
    1. Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK, LiVolsi VA, Papotti MG, Sobrinho-Simões M, Tallini G, Mete O (2022) Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol 33 (1):27-63. https://doi.org/10.1007/s12022-022-09707-3 - DOI - PubMed
    1. Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, Dogan S, Ricarte-Filho JC, Krishnamoorthy GP, Xu B, Schultz N, Berger MF, Sander C, Taylor BS, Ghossein R, Ganly I, Fagin JA (2016) Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. J Clin Invest 126 (3):1052-1066. https://doi.org/10.1172/jci85271 - DOI - PubMed - PMC
    1. Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S, French JD, Borre PV, LaBarbera DV, Tan AC, Schweppe RE, Fishbein L, Ross JS, Haugen BR, Bowles DW (2018) Genetic Analysis of 779 Advanced Differentiated and Anaplastic Thyroid Cancers. Clin Cancer Res 24 (13):3059-3068. https://doi.org/10.1158/1078-0432.Ccr-18-0373 - DOI - PubMed - PMC
    1. Zhang L, Ren Z, Su Z, Liu Y, Yang T, Cao M, Jiang Y, Tang Y, Chen H, Zhang W, Gong R, Wei T, Peng Y, Liu B, Zhang W, Yang L, Hu Y, Li Z, Zhu J, Xu H, Shu Y, Luo H (2021) Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer. J Clin Endocrinol Metab 106 (4):988-998. https://doi.org/10.1210/clinem/dgab014 - DOI - PubMed

Publication types

LinkOut - more resources