Antibody-Based Detection of ERG Rearrangements in Prostate Core Biopsies, Including Diagnostically Challenging Cases ERG Staining in Prostate Core Biopsies

Context.-Fusions of androgen-regulated genes and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) occur in approximately 50% of prostate cancers, encoding a truncated ERG product. In prostatectomy specimens, ERG rearrangements are greater than 99% specific for prostate cancer or high-grade prostatic intraepithelial neoplasia adjacent to ERG-rearranged prostate cancer by fluorescence in situ hybridization and immunohistochemistry. Objective.-To evaluate ERG staining by immunohistochemistry on needle biopsies, including diagnostically challenging cases. Design.-Biopsies from a retrospective cohort (n = 111) enriched in cores requiring diagnostic immunohistochemistry and a prospective cohort from all cases during 3 months (n = 311) were stained with an anti-ERG antibody (clone EPR3864). Results.-Among evaluable cores (n = 418), ERG staining was confined to cancerous epithelium (71 of 160 cores; 44%), high-grade prostatic intraepithelial neoplasia (12 of 68 cores; 18%), and atypical foci (3 of 28 cores; 11%), with staining in only 2 of 162 cores (1%) diagnosed as benign. The ERG was expressed in about 5 morphologically benign glands across 418 cores and was uniformly expressed by all cancerous glands in 70 of 71 cores (99%). Conclusions.-ERG staining is more prostate cancer-specific than alpha-methylacyl-coenzyme A racemase, and staining in an atypical focus supports a diagnosis of cancer if high-grade prostatic intraepithelial neoplasia can be excluded. Thus, ERG staining shows utility in diagnostically challenging biopsies and may be useful in molecularly subtyping prostate cancer and in stratifying isolated high-grade prostatic intraepithelial neoplasia by risk of subsequent cancer. (Arch Pathol Lab Med. 2012;136:935-946; doi: 10.5858/arpa.2011-0424-OA)