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Updated: Nov 26, 2025
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
TROP-2, 5hmC, and IDH1 Expression in Anaplastic Thyroid Carcinoma
Jae Yeon Seok1,2, Kristine Astvatsaturyan2, Mariza De Peralta-Venturina2
1Department of Pathology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.
Background:
Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has no effective treatment to date. Trophoblast cell-surface antigen 2 (TROP-2), a transmembrane glycoprotein, has been suggested to be a promising novel target for sacituzumab govitecan, an antibody-drug conjugate. 5-Hydroxymethylcytosine (5hmC) has a role in tumor suppression and promoting modification. Additionally, isocitrate dehydrogenase 1 (IDH1) mutations are strongly associated with increased overall survival in gliomas and worse prognosis in leukemias. This study attempts to evaluate the immunoexpression of TROP-2, 5hmC, and IDH1 in ATCs and to determine their potential impact in targeted therapy.
Methods:
Twenty-four ATCs were retrieved, with 9 cases that occurred de novo and 15 cases derived from either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma (FTC). Sections were immunostained with TROP-2, 5hmC, and IDH1 antibodies, and evaluated using the QuPath program. The t tests were performed using SPSS software.
Results:
TROP-2 was detected in 12 ATCs with 9 cases demonstrating a high expression and in all PTC components, and absent in all FTC components of secondary ATCs. 5hmC expression was moderately reduced in PTC and FTC components and markedly reduced in ATC. The entire cohort showed a total absence of IDH1.
Conclusions:
Increased TROP-2 immunoexpression in some ATCs supports that these patients may potentially benefit from an antibody-drug conjugate therapy targeting TROP-2. Markedly reduced 5hmC expression suggests that 5hmC may be used as potential therapeutic targets for ATC. The total lack of IDH1 R132H mutation by immunostain indicates that it has no prognostic and therapeutic value in ATC.
Insights
Anaplastic thyroid carcinoma (ATC) shows increased TROP-2 expression, suggesting potential benefit from targeted therapies. Reduced 5-hydroxymethylcytosine (5hmC) indicates its potential as a therapeutic target, while IDH1 mutations were absent.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy with limited treatment options.
- Trophoblast cell-surface antigen 2 (TROP-2) is a potential target for antibody-drug conjugate therapy.
- 5-Hydroxymethylcytosine (5hmC) and isocitrate dehydrogenase 1 (IDH1) mutations have roles in tumor suppression and prognosis.
Purpose of the Study:
- To evaluate the immunoexpression of TROP-2, 5hmC, and IDH1 in ATCs.
- To determine the potential impact of these markers in targeted therapy for ATC.
Main Methods:
- Immunohistochemical staining for TROP-2, 5hmC, and IDH1 on 24 ATC samples (9 de novo, 15 secondary).
- Evaluation of immunoexpression using the QuPath program.
- Statistical analysis using t-tests via SPSS software.
Main Results:
- TROP-2 was detected in 12 ATCs, with high expression in 9 cases and in all papillary thyroid carcinoma (PTC) components; it was absent in follicular thyroid carcinoma (FTC) components.
- 5hmC expression was moderately reduced in PTC/FTC components and markedly reduced in ATC.
- Isocitrate dehydrogenase 1 (IDH1) R132H mutation was completely absent in all analyzed cases.
Conclusions:
- Increased TROP-2 expression in some ATCs suggests potential benefit from TROP-2-targeted antibody-drug conjugate therapy.
- Markedly reduced 5hmC expression indicates its potential as a therapeutic target for ATC.
- The absence of IDH1 R132H mutation suggests it has no prognostic or therapeutic value in ATC.
