Correlation of urine TMPRSS2:ERG and PCA3 to ERG+ and total prostate cancer burden

Abstract

ERG rearrangements (most commonly transmembrane protease, serine 2 [TMPRSS2]:ERG [T2:ERG] gene fusions) have been identified in approximately 50% of prostate cancers . Quantification of T2:ERG in postdigital rectal examination urine, in combination with PCA3, improves the performance of serum prostate-specific antigen for prostate cancer prediction on biopsy. Here we compared urine T2:ERG and PCA3 scores with ERG+ (determined with immunohistochemical analysis) and total prostate cancer burden in 41 mapped prostatectomies. Prostatectomies had a median of 3 tumor foci (range, 1-15) and 2.6 cm of summed linear tumor dimension (range, 0.6-7.1 cm). Urine T2:ERG score correlated most with summed linear ERG+ tumor dimension and number of ERG+ foci (r(s) = 0.68 and 0.67, respectively, both P < .001). Urine PCA3 score showed weaker correlation with both number of tumor foci (r(s) = 0.34, P = .03) and summed linear tumor dimension (r(s) = 0.26, P = .10). In summary, we demonstrate a strong correlation between urine T2:ERG score and total ERG+ prostate cancer burden at prostatectomy, consistent with high tumor specificity.

Figure 1. Mapping ERG+ and ERG− tumor foci in prostatectomy specimens

Prostatectomy specimens (n=41) were mapped, and the index focus and all multifocal foci were identified (see Methods). Immunohistochemistry for ERG was performed on sections representing all index and multifocal foci from each case, and each focus was classified as ERG+ or ERG−. Staining of vessels was used as a positive control and sections without staining of vessels were excluded and staining repeated. A&B. Hematoxylin and eosin (H&E, A) and ERG (B) stained sections of an ERG+ index focus (case 31). Areas of benign glands, HGPIN and carcinoma are indicated by red, blue and black arrows, respectively. C&D. H&E (C) and ERG (D) stained sections of an ERG− multifocal focus (case 6). Endothelial cells and lymphocytes serve as an internal positive control (green arrows). All images are 10× original magnification.

Figure 2. ERG staining is specific for PCa and immediately adjacent HGPIN

ERG staining was evaluated in 169 prostatectomy sections as described in Fig. 1. Across all 169 sections, only one focus of ERG+ high grade prostatic intraepithelial neoplasia (HGPIN) and approximately 2 ERG+ benign glands not immediately adjacent to ERG+ carcinoma were identified. A&B. Hematoxylin and eosin (H&E, A) and ERG (B) stained sections from an ERG− cancer focus showing no expression in cancerous or benign glands. C&D. H&E (C) and ERG (D) stained sections from case 38 demonstrating ERG+ HGPIN not immediately adjacent to cancer. E&F. H&E (E) and ERG (F) stained sections from case 35 demonstrating ERG+ morphologically benign glands not immediately adjacent to cancer. Areas of benign glands, HGPIN and carcinoma are indicated by red, blue and black arrows, respectively. Staining of vessels was used as a positive control.