Molecular pathogenesis of human prostate basal cell hyperplasia

Area of Science:

• Urology
• Molecular Biology
• Pathology

Background:

• Benign prostatic hyperplasia (BPH) therapies target smooth muscle and luminal epithelia, leaving basal cell hyperplasia (BCH) untargeted.
• BCH, occurring in 8-10% of BPH cases, lacks comprehensive molecular and cellular characterization.
• Understanding BPH phenotypes is crucial for improving therapeutic interventions.

Purpose of the Study:

• To molecularly and cellularly characterize basal cell hyperplasia (BCH) in benign prostatic hyperplasia (BPH).
• To investigate the role of the epidermal differentiation complex in BCH.
• To determine if BCH can be classified as a metaplastic condition.

Main Methods:

• RNA-sequencing (RNA-seq) analysis of flow cytometry-purified basal epithelia from BCH and non-BCH patients.
• Quantitative PCR (qPCR) to confirm transcriptomic findings for 28 genes.
• Immunohistochemistry (IHC) to validate protein expression of key genes.

Main Results:

• 141 human BPH specimens were analyzed; BCH showed a significant increase in the basal to luminal epithelia ratio.
• RNA-seq revealed increased expression of epidermal differentiation complex members in BCH basal epithelia.
• IHC confirmed increased protein expression and morphological similarity to other stratified squamous epithelia.

Conclusions:

• Increased epidermal differentiation complex expression and altered epithelial stratification in BCH resemble metaplastic diseases.
• These findings highlight the plasticity of the human prostate epithelium.
• Basal cell hyperplasia (BCH) is proposed to be a metaplastic condition.