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Is there a role for epithelial-mesenchymal transition in adrenocortical tumors?

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Abstract

Purpose

Epithelial-mesenchymal transition (EMT) is a biological dynamic process by which epithelial cells lose their epithelial phenotype and acquire mesenchymal invasive and migratory characteristics. This has been postulated as an essential step during cancer progression and metastasis. Although this is well described in other tumors, the role of EMT in adrenocortical tumors (ACT) has yet to be addressed.

Methods

The aim of this study was to evaluate the expression of EMT markers e-cadherin, vimentin, and fibronectin, along with EMT-transcription factors (EMT-TFs), TWIST1, SIP1, and SNAIL in 24 adrenocortical carcinoma (ACC), 19 adrenocortical adenomas (ACA), 27 childhood-onset adrenocortical tumors (CAT), and 12 normal adrenal glands. The association of EMT and EMT-TFs with clinical outcomes and pathology features were also evaluated.

Results

Cytoplasmic vimentin expression was increased among CAT samples when compared to ACC, ACA, and normal adrenal samples (p < 0.001). There was no difference in e-cadherin and fibronectin expression observed between groups. Nuclear and cytoplasmic expression of TWIST1 and SIP1 was stronger in CAT and ACC vs. ACA and normal tissue samples (all, p < 0.05). ACT, regardless of classification, exhibited increased SNAIL expression when compared to normal tissue (p < 0.05). A significant correlation was observed between vimentin and TWIST1 (r s = 0.44, p < 0.001); SIP1 (r s = 0.51, p < 0.001); and SNAIL (r s = 0.23, p < 0.05). TWIST1 and SIP1 expressions demonstrated a significant correlation (r s = 0.56, p < 0.001). High SIP1 expression was associated with a lower survival rate among ACC cases (p < 0.05).

Conclusions

Vimentin, TWIST1, and SIP1 expressions are increased in aggressive ACT. Therefore, EMT may play a relevant role in adrenal tumorigenesis.

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Acknowledgements

The authors are grateful to Dr. Marisa Dreyer Breitenbach for Institutional support. We are also grateful to Priscila Valverde and Maria Theresa Accioly for technical support with immunohistochemistry reactions.

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This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Authors and Affiliations

  1. Endocrine Oncology Unit, Brazilian National Cancer Institute—INCA, Rio de Janeiro, Brazil

    Daniel Bulzico

  2. Endocrinology Section, Federal Hospital of Lagoa, Rio de Janeiro, Brazil

    Daniel Bulzico, Marcela Pessoa de Paula & Leonardo Vieira Neto

  3. Division of Pathology, Brazilian National Cancer Institute—INCA, Rio de Janeiro, Brazil

    Paulo Antônio Silvestre de Faria & Camila Bravo Maia

  4. Laboratory of Oncovirology, Center for Bone Marrow Transplants, Brazilian National Cancer Institute—INCA, Rio de Janeiro, Brazil

    Davi Coe Torres & Rocio Hassan

  5. Stem cell Laboratory, Center for Bone Marrow Transplants, Brazilian National Cancer Institute—INCA, Rio de Janeiro, Brazil

    Gerson Moura Ferreira, Bruno Ricardo Barreto Pires & Eliana Abdelhay

  6. Department of Internal Medicine and Endocrinology Section, Medical School and Clementino Fraga Filho University Hospital, Rio de Janeiro Federal University, Rio de Janeiro, Brazil

    Mario Vaisman & Leonardo Vieira Neto

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This study was approved by INCA's independent institutional advisory committee in September 24th, 2014 (protocol 33847514.4.0000.5274). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Bulzico, D., Faria, P.S.d., Maia, C.B. et al. Is there a role for epithelial-mesenchymal transition in adrenocortical tumors?. Endocrine 58, 276–288 (2017). https://doi.org/10.1007/s12020-017-1409-z

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