ERG Expression Predicts High-Grade Prostatic Intraepithelial Neoplasia Progression

A gene fusion protein may aid monitoring of men with prostate cancer precursor tissue changes

medwireNews:  Trial findings show that the Gene fusion protein ERG may help identify which men with high-grade prostatic intraepithelial neoplasia (HGPIN) will go on to develop prostate cancer.

The Immunohistochemistry study in 461 men showed that the 11% of patients whose HGPIN biopsy sample expressed the TMPRSS2:ERG gene Translocation were significantly more likely to be diagnosed with prostate cancer during 3 years of follow-up than those with ERG-negative samples (53 vs 35%). The study was a post hoc analysis of a phase III randomised clinical trial in men with biopsy-diagnosed HGPIN who received toremifene or placebo for 3 years or until prostate cancer diagnosis at prostate biopsy.

The recurrent gene fusion is thought to occur early in prostate cancer development and is reported in over 50% of prostate cancers detected by prostate-specific Antigen (PSA) screening, the researchers note.

“What this study shows is that not all HGPIN is equal – that is, clinically significant," commented author Mark Rubin, from Weill Medical College of Cornell University in New York, USA, in a press release.

"When confirmed in larger studies, testing for ERG in these precancerous lesions may change clinical practice in how men are evaluated with abnormal biopsies and may lead to earlier cancer detection."

Kaplan-Meier analysis estimated that 32% of ERG-positive men were free from prostate cancer at 3 years, compared with 56% of ERG-negative patients. The hazard ratio for prostate cancer diagnosis was 0.58 among ERG-negative men relative to ERG-positive men and this was not significantly altered after adjusting for baseline markers such as treatment, PSA velocity, and the presence of atypical small acinar proliferation.

Further analysis showed that ERG expression was not significantly associated with Gleason score, tumour volume or prebiopsy PSA level.

“As a [prostate cancer]-specific gene fusion marker, ERG expression in PIN indicates a neoplastic lesion, highly associated with concurrent cancer, and may imply the presence of undersampled cancer,” the authors write in the Journal of Clinical Oncology.

Mark Rubin et al conclude: “This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression.

“Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification.”

Reference

Park K, Dalton JT, Narayanan R, et al. TMPRSS2:ERG Gene Fusion Predicts Subsequent Detection of Prostate Cancer in Patients With High-Grade Prostatic Intraepithelial Neoplasia. J Clin Oncol 2013 Dec 2. [Epub ahead of print].

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