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Updated: Mar 29, 2026
07:36
Mammosphere Assay Reveals Api5-Induced Stemness in Non-Tumorigenic Breast Epithelial Cell Lines
Published on: February 24, 2026
150
Deciphering Morphological Spectrum, Stemness and PI3K/AKT/PTEN/MAPK Pathway Alterations in Metaplastic Breast
Venkat Shashidhar Chittapragada1, Parul Gupta1, Arvind Sekar1
1Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Summary
Metaplastic breast carcinoma (MBC) shows stem cell markers and actionable PI3K pathway mutations. PI3K inhibitors offer potential targeted therapy for MBC, regardless of subtype.
Area of Science:
- Oncology
- Genomics
- Cancer Stem Cells
Background:
- Metaplastic breast carcinoma (MBC) is a rare, aggressive breast cancer subtype.
- MBC is characterized by distinct morphology and lacks hormone receptor and HER2 expression.
- Tumor cells display epithelial-mesenchymal transition and cancer stem cell traits, suggesting potential therapeutic targets.
Purpose of the Study:
- To investigate the stemness and genomic alterations in MBC.
- To identify targetable mutations within the PI3K/AKT/PTEN/MAPK pathway.
- To correlate findings with MBC histological subtypes.
Main Methods:
- Morphological sub-classification of 67 retrospective MBC cases.
- Evaluation of ALDH1 cytoplasmic expression via immunohistochemistry (IHC) for stemness.
- Next-generation sequencing (NGS) of 47 cases to analyze PI3K/AKT/PTEN/MAPK pathway alterations.
Main Results:
- ALDH1 positivity observed in 31.3% of cases, indicating stemness.
- PI3K pathway alterations were frequent, with PI3K being the most commonly altered gene, followed by PTEN, TP53, and MAPK1.
- PI3K alterations were more prevalent in spindle cell carcinoma and squamous cell carcinoma subtypes.
Conclusions:
- MBC exhibits a high frequency of stem cell markers and targetable genetic alterations in the PI3K signaling pathway.
- Targeted inhibition of the PI3K signaling pathway presents a promising therapeutic strategy for MBC.
- PI3K pathway inhibitors may be effective across diverse MBC histological subtypes.
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