ERG expression in prostate cancer: the prognostic paradox

Area of Science:

• Oncology
• Urology
• Genetics

Background:

• TMPRSS2/ERG fusion leads to ERG overexpression in 30-50% of Caucasian prostate cancer (PCa) cases.
• The prognostic significance of ERG expression in PCa progression remains debated.
• This study investigates ERG expression across all PCa stages and its prognostic impact.

Purpose of the Study:

• To analyze ERG expression in high-grade prostatic intraepithelial neoplasia (PIN), clinically localized PCa (CLC), and castration-resistant PCa (CRPC).
• To evaluate the prognostic value of ERG status in CLC and CRPC.
• To explore ethnic variations in ERG expression.

Main Methods:

• Immunohistochemistry was used to assess ERG and Androgen Receptor (AR) expression.
• Tissue microarrays included samples from high-grade PIN (n=57), CLC (n=299), metastases (n=17), and CRPC (n=41).
• Patients included Caucasians and African-Caribbeans.

Main Results:

• ERG expression increased with PCa progression in Caucasians (17.5% in PIN to 53% in metastases).
• ERG expression was less frequent in African-Caribbeans (11.5%) compared to Caucasians (33%) in CLC.
• In Caucasian CLC, ERG positivity correlated with longer recurrence-free survival.
• In CRPC, ERG expression (29% of cases) was associated with longer overall survival.

Conclusions:

• ERG expression is less common in PCa from patients of African descent.
• Despite increasing with disease progression, ERG positivity is linked to better outcomes in both CLC and CRPC.
• The AR-dependency of ERG may contribute to better response to androgen suppression in ERG-positive tumors.