title: Future directions in the diagnosis and medical treatment of adrenocortical carcinoma.
abstract: Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.
authors.affiliation: Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: S G
authors.initials: SG
authors.lastname: Creemers
authors.affiliation: Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: L J
authors.initials: LJ
authors.lastname: Hofland
authors.affiliation: Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Korpershoek
authors.affiliation: Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: G J H
authors.initials: GJ
authors.lastname: Franssen
authors.affiliation: Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: F J
authors.initials: FJ
authors.lastname: van Kemenade
authors.affiliation: Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: W W
authors.initials: WW
authors.lastname: de Herder
authors.affiliation: Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands Rotterdam Adrenal CenterErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of PathologyErasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of SurgeryErasmus MC University Medical Center, Rotterdam, The Netherlands r.feelders@erasmusmc.nl.
authors.forename: R A
authors.initials: RA
authors.lastname: Feelders
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D000315:Adrenalectomy / Q000379:methods; D018268:Adrenocortical Carcinoma / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D017024:Chemotherapy, Adjuvant; D003940:Diagnostic Techniques, Endocrine / Q000639:trends; D006801:Humans; D008939:Mitotane / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D008939:Mitotane
keywords: adrenocortical cancer; diagnosis; prognostic markers; treatment