Expression of ERG protein, a prostate cancer specific marker, in high grade prostatic intraepithelial neoplasia (HGPIN): Lack of utility to stratify cancer risks associated with HGPIN

Pathology and Laboratory Medicine Institute Glickman Institute of Urology and Kidney, Cleveland Clinic, Cleveland, OH Department of Pathology and Urology, Emory University School of Medicine, Atlanta, GA Department of Pathology, New York University Langone Medical Center, New York, NY, USA Peking University, Health Science Center, Beijing, China.
BJU International (Impact Factor: 3.53). 10/2012; 110(11B). DOI: 10.1111/j.1464-410X.2012.11557.x
Source: PubMed


Study Type – Diagnosis (cohort)
Level of Evidence 2b
What's known on the subject? and What does the study add?
High grade prostatic intraepithelial neoplasia is a pre-malignant lesion to prostate cancer and is associated with 20%–25% risk of prostate cancer in subsequent repeat biopsies. ERG is a highly prostate-cancer-specific marker.
Expression of ERG is rare in isolated high grade prostatic intraepithelial neoplasia diagnosed in prostate biopsy and is not associated with cancer risk in subsequent repeat biopsies.

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Available from: Cristina Magi-Galluzzi, Nov 10, 2014
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    ABSTRACT: TMPRSS2:ERG gene fusions, the most common molecular subtype of ETS family gene fusions occur in ∼50% of prostate carcinomas (PCas) and ∼20% of high-grade prostatic intraepithelial neoplasia (HGPIN) intermingled with adjacent PCa demonstrating identical gene fusions. ERG gene fusions have not yet been demonstrated in isolated benign prostate tissue, isolated high-grade prostatic intraepithelial neoplasia, or benign cancer mimics. Taken together, ERG gene fusions are the most prostate cancer-specific biomarker yet identified and define a specific molecular subtype of PCa with important clinical and biological implications. ERG gene fusions result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG protein product. Recently, N-terminal epitope-targeted mouse (9FY) and C-terminal-targeted rabbit monoclonal (EPR 3864) ERG antibodies are commercially available and are increasingly utilized as a surrogate for TMPRSS2:ERG gene fusions. Until recently, because of lack of availability of reliable ERG antibody, the most commonly utilized methods for studying ERG aberrations in PCa specimens included fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. The knowledge gleaned from these studies has significantly improved our understanding of molecular biology of ERG gene fusions. With availability of highly specific anti-ERG monoclonal antibodies, there are now unprecedented opportunities to explore and validate clinical applications of ERG antibody in routine pathology practice, which has just started. This review provides a brief background of molecular biology of ERG gene fusions in PCa and focuses on characterizing the current state of ERG oncoprotein and determining the role of ERG immunohistochemistry in the diagnosis and biological stratification of prostate cancer.
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    ABSTRACT: Prostate cancer is a heterogeneous, frequently multifocal disease with a broad spectrum of clinical, pathologic, and molecular characteristics. The TMPRSS2-ERG gene rearrangement is highly specific for prostate cancer. We used immunohistochemistry as a surrogate marker of the TMPRSS2-ERG fusion to study the heterogeneity of ERG expression in 280 prostate core needle biopsy series from 256 patients with early prostate cancer defined as 3 or less positive cores with no more than 50% of cancer per biopsy and a Gleason score of 7 or lower (3 + 4). Among the 163 patients with 2 or 3 cancer-positive biopsies, we found a subset of 19 patients (11.7%) with heterogeneous ERG expression. Thirteen (68.4%) of these patients showed biopsies with distinct positive and negative ERG staining in separate cores. The remaining 6 patients showed a mixture of both positive and negative staining within 1 biopsy core. This was either caused by different cancer foci (n = 3) or by one single, ERG-heterogeneous cancer focus (n = 3) in 1 core. Furthermore, we observed a heterogeneous ERG staining pattern over time in 6 (2.3%) of the 256 patients, in biopsies taken at various time points. An interobserver study of 21 cases with 2 separate cancer foci revealed that heterogeneity of ERG status in different cancer foci can be suspected based on morphologic differences (κ = 0.44). We conclude that heterogeneity of ERG expression is detectable in 10% to 15% of core biopsies of early prostate cancer. Further studies are needed to explore the clinical impact of heterogeneous ERG status in this patient group.
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    ABSTRACT: TMPRSS2-ERG is a recurrent rearrangement specific for prostate cancer, leading to the overexpression of a truncated ERG protein product that is amenable to immunohistochemical detection. Two monoclonal anti-ERG antibodies have currently been validated, with comparable sensitivity and specificity for detecting ERG rearrangement. ERG immunostaining has been applied in different settings to elucidate the role of ERG rearrangement and overexpression in prostate cancer tumorigenesis and progression, as well as to investigate potential diagnostic and prognostic applications. In this article we review the literature on the topic and suggest potential future applications.
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