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Immunophenotypic Panel for Comprehensive Characterization of Aggressive Thyroid Carcinomas.
Mihail Ceausu1,2, Mihai Alin Publik1, Dana Terzea1
1Department of Pathology, "C.I. Parhon" National Institute of Endocrinology, 011863 Bucharest, Romania.
Cells
|October 15, 2025
Summary
Aggressive thyroid cancers, including anaplastic (ATC) and poorly differentiated (PDTC), show distinct immunophenotypes. Loss of TTF-1 and PAX-8 markers, along with high Ki-67, indicates aggressive anaplastic transformation.
Area of Science:
- Oncology
- Pathology
- Molecular Biology
Background:
- Aggressive thyroid carcinomas, such as anaplastic (ATC) and poorly differentiated (PDTC), are rare, lethal, and lack standardized diagnostic algorithms.
- Incomplete immunophenotypical characterization hinders effective diagnosis and treatment strategies for these aggressive tumors.
Purpose of the Study:
- To comprehensively characterize the immunophenotype of aggressive thyroid carcinomas (ATC and PDTC).
- To identify diagnostic markers for anaplastic transformation and predict tumor aggressiveness.
- To explore the association between specific mutations (BRAFV600E, TERT) and marker expression.
Main Methods:
- Retrospective analysis of 40 thyroidectomy cases (12 ATC, 28 PDTC) from 2014-2024.
- Evaluation of clinical data, histopathology, molecular analysis (BRAFV600E, TERT mutations), and immunohistochemistry (BRAF, K-RAS, TERT, PAX-8, TTF-1, P53, Ki-67).
Main Results:
- BRAFV600E mutation found in 70% of cases, more in ATC. TERT abnormal expression exceeded 90%.
- Loss of TTF-1 and PAX-8 correlated with anaplastic transformation. Higher Ki-67 indices in ATC indicate aggressiveness.
- Multivariate analysis identified loss of TTF-1 and tumor necrosis as predictors of anaplastic histotype.
Conclusions:
- Immunohistochemistry for BRAFV600E can screen for the mutation. Frequent BRAFV600E and TERT mutations occur, especially in PDTC.
- BRAF/RAF activation, TTF-1/PAX-8 loss, TERT upregulation, and TP53 alterations are common in aggressive thyroid cancers.
- Loss of TTF-1 and necrosis are key indicators for subclassifying aggressive thyroid carcinomas.
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