TY  - EJOU
AU  - Kang, Yu-Ting 
AU  - Hsiao, Tzu-Hung 
AU  - Chen, Yidong 
AU  - Chiang, I-Tien 
AU  - Lee, Li-Wen 
AU  - Phan, Nam Nhut 
AU  - Chen, Wei-Yu 
AU  - Tan, Puay Hoon 
AU  - Chang, Kang-Yu 
AU  - Chen, Wan-Ching 
AU  - Chen, Chih-Jung 

TI  - Spatial Transcriptomic Profiling Identifies Epithelial Heterogeneity and a Potential Lineage-Associated Marker in Breast Mucinous Cystadenocarcinoma
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Background:</b> Breast mucinous cystadenocarcinoma (BMCA) is an ultra-rare primary breast carcinoma classified within the triple-negative breast cancer (TNBC) molecular category. BMCA poses a significant diagnostic challenge because of its morphologic overlap with invasive mucinous carcinoma of the breast and metastatic mucinous carcinomas from the ovary and pancreas. This study aimed to characterize epithelial transcriptional states and identify molecular features with potential diagnostic utility. <b>Methods:</b> High-resolution spatial transcriptomic profiling was performed on three primary BMCA cases using the 10× Genomics Visium HD platform, with a TNBC specimen included as a transcriptomic reference. IHC analysis was performed using pancreatic and ovarian mucinous carcinomas as comparators. <b>Results:</b> Two transcriptionally distinct epithelial tumour populations were identified within BMCA. One population exhibited increased expression of inflammation-associated genes, including S100 calcium-binding protein A8 (<i>S100A8</i>) and S100 calcium-binding protein A8 (<i>S100A9</i>), and was localized to peripheral epithelial regions with limited histological evidence of immune-cell infiltration, suggesting a tumour-associated inflammatory-like state. Pseudotime analysis of Case 2 suggested that Cancer_2 occupied a relatively less differentiated along the inferred transcriptional-state continuum. Across all three BMCA cases, Mucin5B (MUC5B) expression was consistently detected at both transcriptomic and protein levels. IHC analysis demonstrated markedly higher MUC5B expression in BMCA (H-score: 253.3 ± 80.8) than in pancreatic mucinous cystadenocarcinoma (PMCA; 10.0 ± 10.0) and ovarian mucinous cystadenocarcinoma (OMCA; 11.7 ± 11.5). <b>Conclusions:</b> Spatial transcriptomics identified epithelial heterogeneity within BMCA and highlighted MUC5B as a candidate lineage-associated biomarker. Incorporation of MUC5B immunohistochemistry may aid the differential diagnosis of primary BMCA and metastatic mucinous tumours in routine surgical pathology.
KW  - Breast mucinous cystadenocarcinoma; spatial transcriptomics; epithelial heterogeneity; Mucin-5B; diagnostic pathology

DO  - 10.32604/or.2026.081243