Paired-sample Analysis of ERG Expression and TMPRSS2-ERG Fusion in Treatment-induced Neuroendocrine Prostate Cancer

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Prostate cancer frequently develops resistance to androgen deprivation therapy (ADT), leading to castration-resistant prostate cancer (CRPC).
• A subset of CRPC (10-17%) progresses to aggressive, androgen receptor (AR)-independent treatment-induced neuroendocrine prostate cancer (t-NEPC).
• The TMPRSS2-ERG fusion gene is common in prostate cancer, but its role in t-NEPC development is not well understood.

Purpose of the Study:

• To investigate the presence and significance of the TMPRSS2-ERG fusion gene in Japanese cases of t-NEPC.
• To analyze the relationship between ERG expression, AR signaling, and clinical parameters in t-NEPC.

Main Methods:

• Retrospective analysis of nine Japanese t-NEPC cases.
• Immunohistochemical staining for AR and ERG.
• RT-PCR to detect TMPRSS2-ERG fusion gene expression.
• Comparison of clinical data between ERG-positive and ERG-negative groups.

Main Results:

• The TMPRSS2-ERG fusion gene was detected in 33.3% of t-NEPC cases, all of which were AR-positive.
• ERG positivity did not show a clear association with prognosis or drug sensitivity.
• A trend towards shorter time to neuroendocrine differentiation was observed in ERG-positive cases.
• Only the e1e4 isoform of TMPRSS2-ERG was detected.

Conclusions:

• Heterogeneity exists in TMPRSS2-ERG fusion gene dynamics during t-NEPC evolution.
• ERG expression may be associated with earlier neuroendocrine differentiation in prostate cancer.
• This study provides insights into the relationship between ERG, TMPRSS2-ERG fusion, and clinical parameters in t-NEPC.