Aims Widespread use of high-resolution imaging techniques and thus increased prevalence of adrenal lesions has made diagnostics of adrenocortical tumours an increasingly important clinical issue. In non-metastatic tumours, diagnosis is based on histology. New or enhanced information for clinicopathological diagnosis, revealing the malignant potential of the tumour, could emerge by means of biomarkers. The connection of proto-oncogene c-myc to adrenocortical neoplasias is poorly known, although the Wnt/beta-catenin pathway, one of the signalling pathways leading to induction of c-myc expression, has been connected to development of adrenocortical neoplasias. We studied c-myc expression in adrenocortical tumours and investigated molecules associated with the signalling pathway of c-myc, including cell cycle-related proteins p27, cyclin E and cyclin D1.
Methods We studied 195 consecutive adult patients with 197 primary adrenocortical tumours. Histopathological diagnosis was determined by Weiss score and the novel Helsinki score. C-myc, cyclin D1, cyclin E and p27 expressions were determined by immunohistochemistry.
Results Benign adenomas showed prominent nuclear c-myc expression comparable to that of normal adrenocortical cells, whereas carcinomas showed increased cytoplasmic expression. Strong cytoplasmic and weak nuclear c-myc expressions associated with malignancy and adverse outcome. C-myc staining did not correlate with cyclin E. Cyclin D1 correlated with cytoplasmic c-myc expression and to a lesser extent with nuclear c-myc. P27 correlated with cytoplasmic c-myc, but not with nuclear c-myc. P27 correlated with cyclin E.
Conclusions Strong cytoplasmic c-myc expression and weak nuclear expression in adrenocortical tumours associated with malignancy and shorter survival.
- adrenal gland
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JA and CH contributed equally.
Handling editor Cheok Soon Lee.
Contributors MP, IH, TS, JA and CH designed the study. MP, IH and TS collected clinical information of the patients, and IH also operated the majority of the tumours in this study. MP and JA assessed the tumours histologically. MP and JH assessed the immunohistochemical stainings. HM analysed the data statistically. MP and HM interpreted the data. MP drafted the manuscript. JA, CH and TS revised the manuscript. Both JA and CH were the supervisors of the study. All authors read and approved the final manuscript.
Funding This work was supported by grants from the Finnish Cancer Foundation, Sigrid Jusélius Foundation, Helsinki University Hospital Research Fund and Medicinska Understödsföreningen Liv och Hälsa. Funding is obtained from independent scientific foundations. We only have to report scientific results, that is, published papers.
Competing interests None declared.
Ethics approval Ethics Committee of Helsinki University Hospital and the National Supervisory Authority for Welfare and Health.
Provenance and peer review Not commissioned; externally peer reviewed.