Mutational analyses of epidermal growth factor receptor and downstream pathways in adrenocortical carcinoma.

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.

Surgery in adrenocortical carcinoma: Importance of national cooperation and centralized surgery.

BACKGROUND: The low incidence rate of adrenocortical carcinoma (ACC) requires a multidisciplinary approach in which surgery plays an essential role because complete resection of the primary tumor is the only chance of cure. To improve patient care, insight into operative results within the ACC population is essential. In 2007, a Dutch Adrenal Network Registry was created covering care and outcome of patients treated for ACC in the Netherlands since 1965. Using this database, we performed a study (1) to gain insight into surgical performance in the Netherlands and (2) to compare operative data with international literature. METHODS: Data on patients treated from 1965 until January 2008 were studied. The following data were collected: age, gender, functionality of the tumor, stage at diagnosis, operative procedure, completeness of surgery, disease recurrence, adjuvant mitotane therapy, and recurrence-free and overall survival (OS). RESULTS: A total of 175 patients were studied, of whom 149 underwent surgery. Patients with complete resection had significantly longer OS times than patients with incomplete resection (P = .010). Patients operated on in a Dutch Adrenal Network center had significantly longer duration of OS in both univariate (P = .011) and multivariate analysis (P = .014). A significantly greater OS was observed for operated stage IV patients compared with nonoperated patients (P = .002). CONCLUSION: Our data suggest the relevance of national cooperation and centralized surgery in ACC. For selected patients with stage IV disease, surgery can be beneficial in extending survival. On the basis of the retrospective analysis, operative ACC in the Netherlands can and will be improved.