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Increased expression of pro-angiogenic factors and vascularization in thyroid hyperfunctioning adenomas with and without TSH receptor activating mutations

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Abstract

Autonomously functioning thyroid nodules (AFTN) are known to receive an increased blood influx necessary to sustain their high rate of growth and hormone production. Here, we investigated the expression of hematic and lymphatic vases in a series of 20 AFTN compared with the contralateral non-tumor tissues of the same patients, and the transcript levels of proteins involved in the control of vascular proliferation, including the vascular endothelial growth factor (VEGF) and platelet-derived growth factors (PDGF) and their receptors and the endothelial nitric oxide synthase (eNOS). In parallel, the expression of the differentiation markers sodium/iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (Tg), and TSH receptor (TSHR) was also investigated. The data were further analyzed comparing subgroups of tumors with or without mutations in the TSHR gene. Analysis by means of CD31 and D2-40 immunostaining showed in AFTN an increased number of hematic, but not lymphatic, vessels in parallel with an enhanced proliferation rate shown by increased Ki67 staining. Quantitative RT-PCR analysis revealed an increase of VEGF, VEGFR1 and 2, PDGF-A, PDGF-B, and eNOS expression in tumor versus normal tissues. Also, higher transcript levels of NIS, TPO, and Tg were detected. Comparison of the two subgroups of samples revealed only few differences in the expression of the genes examined. In conclusion, these data demonstrate an increased expression of angiogenesis-related factors associated with an enhanced proliferation of hematic, but not lymphatic, vessels in AFTNs. In this context, the presence of TSHR mutations may only slightly influence the expression of pro-angiogenic growth factors.

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Acknowledgments

This work was supported by a grant from Banca d’Italia, Fondazione Umberto Di Mario, and MIUR (PRIN-Cofin 2008). V. Maggisano is fellow of PhD in Pharmaceutical Sciences at the University of Catanzaro.

Conflicts of interest

The authors declare that the experiments comply with the current laws of the country in which they were performed and that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Health Sciences, University of Catanzaro “Magna Graecia”, Viale Europa, Germaneto, 88100, Catanzaro, Italy

    Marilena Celano, Valentina Maggisano & Diego Russo

  2. Department of Internal Medicine and Medical Specialities, University of Roma “Sapienza”, 00161, Rome, Italy

    Marialuisa Sponziello, Mariavittoria Dima, Cosimo Durante & Sebastiano Filetti

  3. Section of Anatomic Pathology, Bellaria Hospital, University of Bologna School of Medicine, 40139, Bologna, Italy

    Giovanni Tallini & Enrico Di Oto

  4. Ospedale di Tinchi-Pisticci, 75100, Matera, Italy

    Rocco Bruno

  5. Department of Surgical Sciences, University of Roma “Sapienza”, 00161, Rome, Italy

    Adriano Redler

  6. Department of Medical Sciences, University of Catanzaro “Magna Graecia”, 88100, Catanzaro, Italy

    Rosario Sacco

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  1. Marilena Celano
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  2. Marialuisa Sponziello
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  3. Giovanni Tallini
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  4. Valentina Maggisano
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  8. Adriano Redler
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  9. Cosimo Durante
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  10. Rosario Sacco
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  11. Sebastiano Filetti
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  12. Diego Russo
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Corresponding author

Correspondence to Diego Russo.

Additional information

Marilena Celano and Marialuisa Sponziello contributed equally to this study.

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Celano, M., Sponziello, M., Tallini, G. et al. Increased expression of pro-angiogenic factors and vascularization in thyroid hyperfunctioning adenomas with and without TSH receptor activating mutations. Endocrine 43, 147–153 (2013). https://doi.org/10.1007/s12020-012-9747-3

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  • DOI: https://doi.org/10.1007/s12020-012-9747-3

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