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

Abstract

E 7 5 1What ' 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-specifi c 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. OBJECTIVES• To evaluate how often ERG, a highly prostate-cancer-specifi c marker, is expressed in isolated high grade prostatic intraepithelial neoplasia (HGPIN) by immunohistochemistry.• To study whether a positive ERG immunostain in HGPIN correlates with prostate cancer (PCa) detection in subsequent repeat biopsies. PATIENTS AND METHODS• Patients with initial HGPIN in biopsies and at least one follow-up prostate biopsy were included.• Biopsies with HGPIN were immunostained for ERG.• The ERG staining results were then correlated with the PCa risk in subsequent biopsies. RESULTS• The mean age of 94 patients was 63 years (range 48 -78). A mean of 1.8 (range 1 -5) repeat biopsy sessions were carried out at a mean interval of 27.4 months (range 1.5 -140). The repeat biopsies showed PCa and non-cancer lesions (benign, HGPIN, atypical glands suspicious for cancer) in 36 patients (38%) and 58 patients (62%) respectively.• ERG immunostain was positive in fi ve (5.3%) biopsies with HGPIN, in which PCa was found in two (40%) subsequent biopsies. Of 89 biopsies with negative ERG staining, PCa was found in 34 (38%) repeat biopsies. The cancer detection rate was not different between ERG positive and negative cases ( P = 0.299). CONCLUSIONS• This is the fi rst study to investigate the ERG protein expression in prostate biopsy containing HGPIN only and its use to stratify the cancer risk associated with HGPIN. We found that ERG expression is distinctly uncommon in isolated HGPIN (5.3%).• Positive ERG expression is not associated with increased cancer detection in subsequent repeat biopsies. The use of ERG immunostain in the evaluation and cancer risk stratifi cation of HGPIN is of limited value.

TMPRSS2:ERG Gene Fusion Predicts Subsequent Detection of Prostate Cancer in Patients With High-Grade Prostatic Intraepithelial Neoplasia

“…Nevertheless, both studies demonstrate higher incidence of cancer after ERG-positive HGPIN. He et al 25 had a cohort of 94 patients with biopsies with isolated HGPIN in which only five patients (5.3%) were ERG positive; no differences were observed in subsequent PCa detection between ERG-positive and ERG-negative patients, but the small study size and few number of ERG-positive patients limit interpretation of these results. From the perspective of a randomized, systemically controlled clinical trial with more than 1,500 patients, our results support that patients with ERG-positive HGPIN are more likely to develop PCa than those with ERG-negative HGPIN.…”

<p>ERG expression in prostate cancer biopsies with and without high-grade prostatic intraepithelial neoplasia: a study in Jordanian Arab patients</p>

“…Generally, studies of cancer-adjacent specimens have shown higher rates of ERG expression: 13%–52% 11–14,16,17. Studies performed on isolated HGPIN have found ERG expression that was lower or even absent: 0–5% 15,38…”

High-Grade Prostatic Intraepithelial Neoplasia and Intraductal Carcinoma With Intraluminal Small Cell Features

“…25 TMPRSS2:ERG gene rearrangement was found to be highly specific for and present in about 50% of prostate cancers and 29% of foci of PIN, according to immunohistochemical staining with anti-ERG antibody that was highly correlated with TMPRSS2:ERG gene rearrangement status. 29 Conversely, He and colleagues 30 found 38% risk of cancer on repeat biopsy that was independent of ERG staining status with PIN. 27 In a prospective study of ERG staining of biopsies with PIN, Gao and colleagues 28 found that this marker was highly predictive of cancer on repeat biopsy (95% in positive cases vs 5% in negative cases).…”