Abstract Introduction Mucinous carcinoma (MC) of the breast is histologically defined by the World Health Organization as either pure (comprising 90% mucinous component) or mixed (comprising 10-90% mucinous component) subtypes. Typically, the tumor nests within MC display conventional cluster morphology or invasive micropapillary carcinoma (IMPC) architecture. Intriguingly, some MCs contain hypercellular solid nests with neuroendocrine features that closely resemble solid papillary carcinoma (SPC), a distinct entity characterized by mucin production and fibrovascular cores. Given the overlapping morphological and secretory features between SPC and some forms of MCs, we hypothesized that a subset of MCs may arise from or share a lineage with SPC. To explore this, we stratified MCs based on the presence or absence of SPC-like histological features and conducted a comprehensive molecular characterization using data from The Cancer Genome Atlas Breast Invasive Carcinoma Collection (TCGA-BRCA). This study aims to elucidate the biological distinctions between SPC-related and non-SPC MC subtypes, potentially refining our understanding of MC heterogeneity and its clinical implications. Material 10% mucinous component were selected and subclassified into two groups based on histopathological features: those with a SPC component (MC-SPC) and those without a SPC component, including IMPC patterns (MC-OTHER). Clinicopathological parameters were collected and compared between the groups using the chi-square or Fisher's exact test, as appropriate. To explore transcriptional differences, differentially expressed genes (DEGs) were identified using a false discovery rate-adjusted p-value 0.05 and an absolute log2 fold change 1. DEGs were visualized using principal component analysis (PCA), volcano plots, and heatmaps. Functional enrichment analyses were performed using the clusterProfiler R package, referencing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. R (version 4.4.3) was used for all statistical analyses. [Result We identified 29 mucinous carcinoma cases from the TCGA-BRCA cohort with 10% mucinous component, including 18 with MC-SPC and 11 with MC-OTHER. The median age was 67.5 years (range, 41-85) in the MC-SPC group and 55 years (range, 38-79) in the MC-OTHER group. There was no significant difference in age between the two groups (p = 0.16). The HER2-positive subtype was significantly more frequent in MC-OTHER compared to MC-SPC (p = 0.014). Transcriptomic analysis revealed distinct molecular profiles between the two groups, as demonstrated by volcano plots and a heatmap of the top 30 differentially expressed genes, although PCA did not show clear separation. Functional enrichment analysis showed that MC-OTHER tumors exhibited upregulation of pathways related to extracellular matrix (ECM) organization and cell adhesion, suggesting a more mesenchymal-like phenotype. In contrast, MC-SPC tumors were enriched for pathways associated with synaptic signaling and neurotransmitter transport, reflecting potential neuroendocrine-associated biology. Conclusion This study identifies two transcriptionally distinct subtypes of mucinous carcinoma, MC-SPC and MC-OTHER, based on histopathological features. These subtypes exhibit divergent biological characteristics, including mesenchymal-like features in MC-OTHER and neuroendocrine-associated pathways in MC-SPC. This subclassification may have clinical relevance and warrants further investigation in larger cohorts. Citation Format: Y. Hara, R. Yamaguchi, M. Matsumoto, M. Oshi, S. Urakawa, A. Tanaka, M. Akashi, S. Kuba, R. Otsubo, S. Eguchi, K. Matsumoto. Distinct Biological Profiles of Mucinous Carcinoma with a Solid Papillary Carcinoma Component Compared to Other Histological Types abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-05-18.
Hara et al. (Tue,) studied this question.