Endocrine Pathology

, Volume 28, Issue 4, pp 326–331 | Cite as

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

  • Daniel BulzicoEmail author
  • Davi Coe Torres
  • Gerson Moura Ferreira
  • Bruno Ricardo Barreto Pires
  • Paulo Antônio Silvestre de Faria
  • Rocio Hassan
  • Eliana Abdelhay
  • Mario Vaisman
  • Leonardo Vieira Neto


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.


Adrenocortical carcinoma TWIST1 SIP1 TP53 Mutation 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Daniel Bulzico
    • 1
    • 2
    Email author
  • Davi Coe Torres
    • 3
  • Gerson Moura Ferreira
    • 4
  • Bruno Ricardo Barreto Pires
    • 4
  • Paulo Antônio Silvestre de Faria
    • 5
  • Rocio Hassan
    • 3
  • Eliana Abdelhay
    • 4
  • Mario Vaisman
    • 6
  • Leonardo Vieira Neto
    • 2
    • 6
  1. 1.Endocrine Oncology UnitBrazilian National Cancer Institute—INCARio de Janeiro/RJBrazil
  2. 2.Endocrinology SectionFederal Hospital of LagoaRio de JaneiroBrazil
  3. 3.Laboratory of Oncovirology, Center for Bone Marrow TransplantsBrazilian National Cancer Institute—INCARio de JaneiroBrazil
  4. 4.Stem Cell Laboratory, Center for Bone Marrow TransplantsBrazilian National Cancer Institute – INCARio de JaneiroBrazil
  5. 5.Division of PathologyBrazilian National Cancer Institute – INCARio de JaneiroBrazil
  6. 6.Department of Internal Medicine and Endocrinology Section—Medical School and Clementino Fraga Filho University HospitalRio de Janeiro Federal UniversityRio de JaneiroBrazil

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