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PDCD4 expression in thyroid neoplasia

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Abstract

Both the morphogenesis and the molecular pathways of thyroid cancers are controversial. Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is controlled by miR-21. By applying immunohistochemistry for PDCD4 and both quantitative real-time PCR (qRT-PCR) and in situ hybridization for miR-21, this study explored PDCD4 expression in human follicular-cell-derived thyroid neoplastic lesions. PDCD4 protein expression was semiquantitatively assessed in 100 consecutive thyroid tumors (25 follicular adenomas (FA), 25 follicular carcinomas (FC), 25 papillary carcinomas (PC), and 25 poorly-differentiated/anaplastic cancers (PD-AC)). Twenty-five additional nonneoplastic thyroid tissue samples were included as controls. To further support the data, miR-21 expression was tested (by qRT-PCR and in situ hybridization) in a different series of 75 cases (15 FAs, 15 FCs, 15 PCs, 15 PD-ACs, and 15 controls). Nonneoplastic thyrocytes consistently featured a strong nuclear PDCD4 expression, while the protein’s expression was significantly downregulated in neoplastic epithelia. PDCD4 downregulation was significantly associated with less well-differentiated cancer phenotypes (p < 0.001) and more advanced tumor stages (p < 0.001). Consistently with PDCD4 downregulation, miR-21 was upregulated in neoplastic by comparison with nonneoplastic tissue samples. The present results provide evidence of PDCD4 having a role in thyroid carcinogenesis; further studies should investigate the diagnostic value and the prognostic impact of PDCD4 in thyroid neoplasia.

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Abbreviations

nN:

Nonneoplastic thyroid tissue

FA:

Follicular adenoma

PC:

Papillary carcinoma

FC:

Follicular carcinoma

PD-AC:

Poorly-differentiated and anaplastic carcinoma

PDCD4:

Programmed cell death 4

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Acknowledgments

This work was supported by an AIRC Regional grant 2008 (assigned to M.R.). The authors are grateful to Vanni Lazzarin and Cristiano Lanza for their technical assistance.

Conflict of interest

The authors have no competing interests to declare.

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Authors and Affiliations

  1. Department of Medicine (DIMED), Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy

    Gianmaria Pennelli, Matteo Fassan, Marco Pizzi, Mariangela Balistreri, Francesca Galuppini, Vincenza Guzzardo & Massimo Rugge

  2. Department of Surgical Oncology and Gastroenterology Sciences (DiSCOG), General Oncology Unit, University of Padua, Padua, Italy

    Matteo Fassan

  3. Department of Medicine (DIMED), Endocrinology Unit, University of Padua, Padua, Italy

    Caterina Mian & Susi Barollo

  4. Department of Surgical Oncology and Gastroenterology Sciences (DiSCOG), Surgery Unit, University of Padua, Padua, Italy

    Mariarosa Pelizzo

  5. Istituto Oncologico del Veneto, IOV-IRCCS, Via Aristide Gabelli, 61, 35121, Padua, Italy

    Massimo Rugge

Authors
  1. Gianmaria Pennelli
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  2. Matteo Fassan
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  3. Caterina Mian
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  4. Marco Pizzi
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  5. Mariangela Balistreri
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  6. Susi Barollo
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  7. Francesca Galuppini
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  8. Vincenza Guzzardo
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  9. Mariarosa Pelizzo
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  10. Massimo Rugge
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Corresponding author

Correspondence to Massimo Rugge.

Additional information

Gianmaria Pennelli and Matteo Fassan contributed equally to this work.

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Pennelli, G., Fassan, M., Mian, C. et al. PDCD4 expression in thyroid neoplasia. Virchows Arch 462, 95–100 (2013). https://doi.org/10.1007/s00428-012-1352-6

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  • DOI: https://doi.org/10.1007/s00428-012-1352-6

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