Adrenocortical carcinoma: From genomics to patients.

BACKGROUND

Adrenocortical carcinoma (ACC) is a rare malignancy with limited therapeutic options and poor prognosis in advanced stages. Clinico-pathological markers, such as Ki67 and ENSAT stage remain insufficient to fully predict recurrence or treatment response, highlighting the need for molecular characterization.

MOLECULAR CLASSIFICATION: Omic approaches, including transcriptomics, DNA methylation and chromosomal alteration profiling have consistently identified two distinct ACC subtypes "C1A" and "C1B". C1A tumors, overexpressing proliferation genes, are associated to poorer outcomes. C1B tumors however, are characterized by their immune signature and are of better prognosis. Single-cell analyses have helped understanding the mechanisms underlying these differences, hinting at a central role of intratumoral steroid differentiation in shaping the immune microenvironment.

CLINICAL AND THERAPEUTIC PERSPECTIVES: Transcriptome sequencing from paraffin-embedded samples are bringing molecular classification closer to routine care, with ongoing prospective trials evaluating its feasability. Genomic classification represents a major step in ACC management and understanding, offering improved prognostic stratification and orienting future therapeutic strategies.