ERG Immunohistochemistry Combined with CK5/6 and AMACR in Prostate Needle Biopsy Evaluation
Sandra L Lee, Cheng Wang, Saba Raya, Liu Shuhong, Kiril Trpkov, Tarek A Bismar. University of Calgary, Calgary Laboratory Sevices, Calgary, AB, Canada
Background: Gene rearrangements involving the ETS gene family, most commonly fusions between ERG and TEMPRSS2, are found in 40-60% of prostate cancer (PCA) from surgical cohorts. ERG protein can be detected using immunohistochemistry (IHC), and in addition to AMACR and basal cell markers, may add diagnostic value to the work-up of prostate needle biopsies (PNB).
Design: We studied PNB signed out prospectively in our institution during a 6 month period (119 biopsies from 71 patients) in which dual AMACR-CK (Cytokeratin) 5/6 IHC had been performed due to diagnostic difficulty. In addition, 16 cases with Gleason Score (GS) ≥7 were also included to further investigate the relationship between ERG and GS. ERG IHC was examined on the same foci evaluated by AMACR-CK5/6. IHC staining for ERG, AMACR, and CK5/6 was assessed in PCA, high grade prostatic intraepithelial neoplasia (HGPIN), HGPIN with adjacent atypical glands (PINATYP) and atypical/suspicious (ATYP) foci, and benign mimickers of PCA. We also recorded the GS for the cores with PCA, the overall GS for the PNB, presence of HGPIN, extraprostatic extension, perineural invasion, bilateral PCA involvement, the percent of PCA in the core with the largest involvement, and the overall percent of PCA.
Results: We evaluated 70 foci of PCA, of which 38 (54%) were minimal PCA, 45 HGPIN foci, 31 PINATYP and ATYP foci, and 31 foci of benign mimickers of PCA. ERG was positive in 36% of PCA, 27% of HGPIN, 13% of ATYP and PINATYP, and 0% of benign mimickers. ERG positive HGPIN was strongly associated with ERG positive PCA in the same core (p<0.0001). ERG positive PCA showed trends towards higher tumor volume compared to ERG negative PCA, including increased incidence of bilateral disease, increased total tumor volume, increased mean PCA per core, and increased number of positive cores. ERG expression in PCA had an inverse relationship with GS. GS 6, 7 and 8 had, 50%, 28%, and 22% ERG positivity, respectively. ERG was more specific for PCA than AMACR (0.87 versus 0.23), but it was less sensitive (0.36 versus 0.95).
Conclusions: ERG IHC has limited diagnostic value which is restricted to specific scenarios (e.g. mostly when there is an AMACR negative suspicious focus or rare foci of PCA which may be basal cell marker positive). ERG positive HGPIN may have clinical significance because it is strongly associated with ERG positive PCA in the same core. ERG was more commonly found in PCA with lower GS and ERG positive PCA demonstrated trends towards higher tumor volume.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 140, Monday Morning