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A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive Adrenocortical Carcinoma

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Abstract

Adrenocortical carcinomas (ACC) are very rare tumors related to TP53 mutations mostly in childhood onset cases. Epithelial-mesenchymal transition (EMT) transcription factors TWIST1 and Smad interacting protein 1 (SIP1) are related to poorer outcomes in other malignancies, but their role in ACC is unknown. We describe a case of an advanced metastatic ACC (Weiss-score of 9) in a patient at age 76. After primary tumor resection, mitotane therapy was started as palliation to low-volume liver metastasis. After a 2-year period of stable disease, the patient died due to brain metastasis. Somatic gene sequencing revealed a novel TP53 mutation in DNA extracted from paraffin-embedded tissue, a deletion of 8bp in exon 8 (c.811_818del8; GAGGTGCG/−) in homo or hemizygosis causing a subsequent frameshift and premature stop codon at position 302. Immunohistochemistry of P53 and p-Ser-15 P53 showed absent tumoral staining. In addition, immunohistochemical analysis showed an increased expression of the mesenchymal markers vimentin and fibronectin. At last, EMT transcription factors TWIST1 and SIP1 were also overexpressed in tumoral cells. This case report describes an aggressive ACC with not only a novel somatic mutation, but also a novel International Agency for Research on Cancer database 8 base-pair deletion in TP53 exon 8. In addition, the expression of EMT inducers TWIST1 and SIP1 have been reported for the first time in an ACC case. Further investigation is needed to clarify the biologic significance of this new TP53 mutation and its role in the EMT process.

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Authors and Affiliations

  1. Endocrine Oncology Unit, Brazilian National Cancer Institute—INCA, Praça da Cruz Vermelha, 23, 8th floor, Rio de Janeiro/RJ, CEP 20.230-130, Brazil

    Daniel Bulzico

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

    Daniel Bulzico & Leonardo Vieira Neto

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

    Davi Coe Torres & Rocio Hassan

  4. 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

  5. Division of Pathology, Brazilian National Cancer Institute – INCA, Rio de Janeiro, Brazil

    Paulo Antônio Silvestre de Faria

  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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  1. Daniel Bulzico
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Correspondence to Daniel Bulzico.

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The authors declare that they have no conflict of interest.

Funding

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

Ethical Approval

This study was approved by INCA’s independent institutional advisory committee in September 24th, 2014 (protocol 33847514.4.0000.5274). All procedures performed in the study involving the reported case 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., Torres, D.C., Ferreira, G.M. et al. A Novel TP53 Mutation Associated with TWIST1 and SIP1 Expression in an Aggressive Adrenocortical Carcinoma. Endocr Pathol 28, 326–331 (2017). https://doi.org/10.1007/s12022-017-9482-7

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