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- Title
Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma.
- Authors
Hermsen, Ilse G. C.; Haak, Harm R.; de Krijger, Ronald R.; Kerkhofs, Thomas M. A.; Feelders, Richard A.; de Herder, Wouter W.; Wilmink, Hanneke; Smit, Jan W. A.; Gelderblom, Hans; de Miranda, Noel F. C. C.; van Eijk, Ronald; van Wezel, Tom; Morreau, Hans
- Abstract
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 one-third of all malignancies. EGFR pathway members in ACC have been investigated, however, without available clinical data and relation to survival. Methods: In this 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 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) and 11 TP53, 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 on 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.
- Subjects
THERAPEUTICS research; EPIDERMAL growth factor receptors; IMMUNOHISTOCHEMISTRY; GENETIC mutation; PROTEIN-tyrosine kinases
- Publication
European Journal of Endocrinology, 2013, Vol 169, Issue 1, p51
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-13-0093