open access

Vol 67, No 4 (2016)
Review article
Published online: 2016-07-06
Submitted: 2016-03-15
Accepted: 2016-05-02
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Molecular pathways of human adrenocortical carcinoma — translating cell signalling knowledge into diagnostic and treatment options

Paulina Szyszka, Ashley B. Grossman, Salvador Diaz-Cano, Krzysztof Sworczak, Dorota Dworakowska
DOI: 10.5603/EP.a2016.0054
·
Endokrynologia Polska 2016;67(4):427-450.

open access

Vol 67, No 4 (2016)
Review article
Published online: 2016-07-06
Submitted: 2016-03-15
Accepted: 2016-05-02

Abstract

Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/– chemotherapy) are limited, and the results remain unsatisfactory.

Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene.

The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith-Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools.

In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches. (Endokrynol Pol 2016; 67 (4): 427–440)

Abstract

Adrenocortical carcinoma is associated with a low cure rate and a high recurrence rate. The prognosis is poor, and at diagnosis 30-40% of cases are already metastatic. The current therapeutic options (surgical resection, followed by adjuvant mitotane treatment +/– chemotherapy) are limited, and the results remain unsatisfactory.

Key molecular events that contribute to formation of adrenocortical cancer are IGF2 overexpression, TP53-inactivating mutations, and constitutive activation of the Wnt/b-catenin signalling pathway via activating mutations of the b-catenin gene.

The underlying genetic causes of inherited tumour syndromes have provided insights into molecular pathogenesis. The increased occurrence of adrenocortical tumours in Li-Fraumeni and Beckwith-Wiedemann syndromes, and Carney complex, has highlighted the roles of specific susceptibility genes: TP53, IGF2, and PRKAR1A, respectively. Further studies have confirmed that these genes are also involved in sporadic tumour cases. Crucially, transcriptome-wide studies have determined the differences between malignant and benign adrenocortical tumours, providing potential diagnostic tools.

In conclusion, enhancing our understanding of the molecular events of adrenocortical tumourigenesis, especially with regard to the signalling pathways that may be disrupted, will greatly contribute to improving a range of available diagnostic, prognostic, and treatment approaches. (Endokrynol Pol 2016; 67 (4): 427–440)

Get Citation

Keywords

adrenocortical carcinoma; adrenal cortex neoplasms; molecular pathology; signal transduction pathways; hereditary neoplastic syndromes; molecular targeted therapy

About this article
Title

Molecular pathways of human adrenocortical carcinoma — translating cell signalling knowledge into diagnostic and treatment options

Journal

Endokrynologia Polska

Issue

Vol 67, No 4 (2016)

Pages

427-450

Published online

2016-07-06

DOI

10.5603/EP.a2016.0054

Bibliographic record

Endokrynologia Polska 2016;67(4):427-450.

Keywords

adrenocortical carcinoma
adrenal cortex neoplasms
molecular pathology
signal transduction pathways
hereditary neoplastic syndromes
molecular targeted therapy

Authors

Paulina Szyszka
Ashley B. Grossman
Salvador Diaz-Cano
Krzysztof Sworczak
Dorota Dworakowska

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