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Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma
Ilse G C Hermsen1, Harm R Haak, Ronald R de Krijger
1Department of Internal Medicine, Máxima Medical Centre, PO Box 90052, 5600 PD Eindhoven, The Netherlands. ilsehermsen@gmail.com
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.2590> 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.
Insights
Predictive factors for mitotane response in adrenocortical carcinoma (ACC) were investigated. Epidermal growth factor receptor (EGFR) mutations and pathway signaling did not correlate with mitotane treatment outcomes or survival in ACC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis and limited treatment options.
- Mitotane is the standard first-line therapy, but only 30% of patients respond.
- Identifying predictive factors for mitotane response is crucial for improving ACC treatment.
Purpose of the Study:
- To investigate the role of epidermal growth factor receptor (EGFR) pathway mutations in predicting mitotane response and survival in adrenocortical carcinoma (ACC).
- To evaluate the clinical significance of EGFR and downstream signaling pathway mutations in ACC patients treated with mitotane.
Main Methods:
- Mutation status of EGFR and downstream pathways was analyzed in 47 ACC patients using direct sequencing, TaqMan assays, and immunohistochemistry.
- Analysis utilized archival formalin-fixed paraffin-embedded tumor tissue.
- Patient data were anonymized and linked to tumor tissue samples.
Main Results:
- Mutations were identified in BRAF (1), EGFR TK domain (2), and TP53 (11). No PIK3CA or KRAS mutations were found.
- No significant correlation was observed between mutation status, immunostaining results, and mitotane response.
- Tumor mutational status did not predict patient survival in this cohort.
Conclusions:
- The study suggests a limited role for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in treating adrenocortical carcinoma (ACC).
- EGFR monoclonal antibody therapy may offer potential benefits for a larger subset of ACC patients.
- Further clinical trials are warranted to evaluate the efficacy of EGFR-targeted therapies in ACC.
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