BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis and limited therapeutic options.
Mitotane is considered the standard first line therapy with only 30% of the patients showing objective tumour response. Defining predictive factors for response is therefore of clinical importance.The Epidermal Growth Factor Receptor (EGFR) has been implicated in the development of 1/3 of all malignancies. EGFR pathway members in ACC have been investigated, however without available clinical data and relation to survival.
METHODS: In the present study mutation status of EGFR and downstream signalling pathways was evaluated in 47 ACC patients on mitotane using direct sequencing, a TaqMan allele-specific assay and immunohistochemistry. Archival formalin-fixed paraffin-embedded tumour tissue (FFPE) was used for all analyses. Patient data were obtained anonymously, after coupling with the collected tumour tissue.
RESULTS: One BRAF, two EGFR TK domain (c.2590G >A, p.864A >T), 11TP53, but no PIK3CA or KRAS mutations were found. No relationship was found between mutation status, immunostaining and mitotane response or survival.
CONCLUSION: In conclusion, our data suggest that the role of EGFR Tyrosine Kinase inhibitors in ACC is limited. Treatment with EGFR monoclonal antibodies in the other hand might be beneficial for a larger group of patients. The possible efficacy of this therapy in ACC should be evaluated in future trials.
Written by:
Hermsen I, Haak HR, de Krijger RR, Kerkhofs T, Feelders RA, de Herder W, Wilmink H, Smit JW, Gelderblom H, Mirande ND, Eijk R, Wezel TV, Morreau H. Are you the author?
I Hermsen, Internal Medicine, MMC Eindhoven, Eindhoven, 5631 BM, Netherlands.
Reference: Eur J Endocrinol. 2013 Apr 12. Epub ahead of print.
doi: 10.1530/EJE-13-0093
PubMed Abstract
PMID: 23585556
UroToday.com Investigative Urology Section
