Transcriptomic alterations underlying metaplasia into specific metaplastic components in metaplastic breast carcinoma

Area of Science:

• Oncology
• Genomics
• Molecular Pathology

Background:

• Metaplastic breast carcinoma (MpBC) is characterized by carcinoma of no special type (NST) and diverse metaplastic elements.
• Previous studies noted subtype heterogeneity, but intracase transcriptomic differences between metaplastic and NST components remain unclear.

Purpose of the Study:

• To investigate the intracase transcriptomic alterations between metaplastic and paired NST components in MpBC.
• To elucidate the molecular mechanisms driving metaplasia in MpBC.

Main Methods:

• Microdissection of 59 NST and paired metaplastic components (spindle, matrix-producing, rhabdoid, squamous) from 27 MpBC patients.
• Gene expression profiling using the NanoString Breast Cancer 360 Panel.

Main Results:

• Metaplastic components showed subtype-dependent gene expression profiles (GEPs).
• Spindle carcinomatous (SPS) components exhibited upregulation of stem cell and EMT-related genes.
• Rhabdoid (RHA) components showed vascular endothelial growth factor signaling enrichment; squamous carcinomatous (SQC) components showed TGF-β and cell adhesion gene upregulation.
• NST components' intrinsic signatures correlated with metaplastic type, predicting metaplastic subtype with 74.2% accuracy.
• EMT activity and stem cell traits in NST components correlated with lymph node metastasis.

Conclusions:

• Distinct transcriptomic alterations underlie specific metaplastic components in MpBC.
• These findings advance the understanding of MpBC pathogenesis and metaplastic processes.