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Gene expression of thyroid-specific transcription factors may help diagnose thyroid lesions but are not determinants of tumor progression

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Abstract

Purpose

The role of thyroid-specific transcription factors in thyroid malignancy is still poorly understood, so we investigate thyroid-specific transcription factors gene expression both in benign and in malignant thyroid nodules, aiming to study a possible clinical utility of these molecules.

Methods

We quantified TTF-1, FOXE1 and PAX8 mRNA levels, relating their expression to diagnostic and prognostic features of thyroid tumors. RNA was extracted from 4 normal thyroid tissues, 101 malignant [99 papillary thyroid carcinomas (PTC) and 2 anaplastic thyroid carcinomas] and 99 benign thyroid lesion tissues [49 goiter and 50 follicular adenomas (FA)].

Results

Levels of mRNA of both FOXE1 (P < 0.0001) and PAX8 (P < 0.0001) genes, but not TTF-1 (P = 0.7056), were higher in benign than in malignant thyroid lesions. FOXE1 was able to identify malignant nodules with 75.8 % sensitivity, 76.1 % specificity, 75.8 % positive predictive value, 76.1 % negative predictive value and 75.9 % accuracy. PAX8 was able to identify malignancy with 60.6 % sensitivity, 81.1 % specificity, 76.9 % positive predictive value, 66.4 % negative predictive value and 70.6 % accuracy. Both FOXE1 and PAX8 gene expression patterns were also able to differentiate FA from the follicular variant of PTC-FVPTC. However, the investigated gene expression was neither associated with any clinical feature of tumor aggressiveness nor associated with recurrence or survival.

Conclusions

We suggest that FOXE1 and PAX8 gene expression patterns may help to diagnose thyroid nodules, identifying malignancy and characterizing follicular-patterned thyroid lesions, but are not determinants of thyroid tumor progression.

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Acknowledgments

The authors thank Etna Macário for the language services provided. A special thank to our group from the Laboratory of Cancer Molecular Genetics (GEMOCA) of the School of Medical Sciences.

Funding

This study received financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Grant # 2013/18683-7.

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Correspondence to F. A. Batista.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Consent has been obtained from each patient after full explanation of the purpose and nature of all procedures.

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Batista, F.A., Ward, L.S., Marcello, M.A. et al. Gene expression of thyroid-specific transcription factors may help diagnose thyroid lesions but are not determinants of tumor progression. J Endocrinol Invest 39, 423–429 (2016). https://doi.org/10.1007/s40618-015-0386-4

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  • DOI: https://doi.org/10.1007/s40618-015-0386-4

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