Endocrine Abstracts

Adrenocortical carcinoma (ACC) is a rare aggressive endocrine cancer with a heterogeneous prognosis and limited treatment options. Initial tumor stage, resection status and Ki67 index are established clinical/histopathological prognostic factors, but do not always predict clinical outcome. Combined scores have been therefore proposed to improve prognostication of ACC. Hereby, the S-GRAS score has proved to have the best prognostic performance. Genome-wide multi-omics studies identified molecular patterns associated with poor prognosis, but required cost-intensive technologies and complex workup, precluding the adoption of the proposed prognostic biomarkers into clinical practice. More recently, targeted next-generation sequencing (NGS) has been validated for calling mutations, chromosome alterations and DNA methylation status in ACC samples. Still, all these studies were performed with snap-frozen samples that are not always available in clinical settings. In a retrospective project, we used DNA isolated from formalin-fixed paraffin-embedded (FFPE) specimens, readily available in clinical settings We applied targeted NGS for investigating alterations in 160 cancer-related genes and pyrosequencing for methylation in four genes and demonstrated that molecular profiling may improve prognostication of ACC. In following studies, we showed that the number of relevant genes relevant can be reduced to less than 10, making targeted sequencing even more applicable in clinical practice, paving the way towards precision medicine. It is now the task to prove that proposed techniques are feasible in real-life setting and biomarkers are clinically helpful to guide clinicians in patient care. Another important towards optimized management of patients with ACC would be the investigation of molecular alterations in circulating cell-free tumor DNA (ccfDNA). Previous studies showed that ccfDNA can be detected in a subset of patients and could be used for both prediction of clinical outcome and detection of early disease recurrences. Its application as prognostic biomarker or monitoring tool in clinical practice remain to be determined.