DNA methylation is an independent prognostic marker of survival in adrenocortical cancer.

Context:Adrenocortical cancer (ACC) is an aggressive tumor with heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67 index. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival.Objective:To confirm the prognostic value of CpG islands methylation on an independent cohort with a single commonly available methylation assay.Design:CpG islands methylation was measured by methylation-specific-multiplex-ligation-dependent-probe-amplification (MS-MLPA) using the ME002 kit (MRC-Holland).Setting:MS-MLPA was performed in a training cohort of 50 ACC to identify the best set of probes correlating with disease-free (DFS) and overall survival (OS). These were then validated in an independent cohort from 21 ENSAT centers.Patients:The validation cohort included 203 ACC: 64% females, median age 50 years, 80% localized tumors.Intervention:None.Main Outcome Measures:DFS and OS (Cox models).Results:In the training ...