Molecular dichotomy of mucinous carcinoma defined by the presence of solid papillary carcinoma components: an...

Mucinous carcinoma (MC) of the breast is a relatively homogeneous entity; however, it may occasionally display invasive micropapillary features. A subset of cases also show histological overlap with solid papillary carcinoma (SPC), suggesting potential biological divergence. In this study, we performed an integrative transcriptomic analysis of MC using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts to investigate the molecular significance of SPC-associated features.

MC cases were stratified into those with SPC components (MC-SPC) and those without SPC components (MC-OTHER) based on histological assessment in the TCGA cohort and transcriptomic scoring in the METABRIC cohort. In TCGA cohort, MC-SPC was enriched for neurotransmission and synaptic signalling pathways, whereas MC-OTHER demonstrated upregulation of extracellular matrix organization and cell adhesion. These findings were replicated in the METABRIC cohort by using a projected SPC-like gene signature. After adjusting for immune-related confounding factors, distinct immune and metabolic profiles emerged: OTHER-like MCs were associated with increased immune signalling, whereas SPC-like MCs exhibited enhanced mitochondrial and biosynthetic activities.

These findings indicate that MC comprises at least two biologically and histologically distinct variants defined by SPC-associated features, providing a framework for refined classification and development of subtype-specific therapeutic strategies.