Multi-omics integration unravels four molecular subgroups of corticotroph pituitary neuroendocrine tumours with distinct clinicopathological

Corticotroph pituitary neuroendocrine tumours (PitNETs)/adenomas are heterogeneous sellar neoplasms that lack a widely accepted molecular-based classification. The researchers compiled molecular data from 270 corticotroph PitNETs, encompassing epigenome, transcriptome, and proteome profiles. Comprehensive integrative analyses were performed to identify, validate, and characterise definitive molecular subgroups. Corticotroph PitNETs are separated into four robust and clinicopathologically distinct molecular subgroups, which can be broadly distinguished by microscopy using SSTR1, GATA3, and SSTR5 immunohistochemistry. An integrated stratification model incorporating these molecular subgroups demonstrates significant prognostic utility. The findings support the establishment of a refined molecular-based corticotroph PitNET classification, which will require validation in prospective studies. To facilitate future research, an easy-to-use epigenomic classifier for corticotroph PitNETs is provided.