The diagnostic use of ERG in resolving an "atypical glands suspicious for cancer" diagnosis in prostate biopsies beyond that provided by basal cell and α-methylacyl-CoA-racemase markers

Immunohistochemical (IHC) staining for ERG is used as a surrogate for TMPRSS2-ERG gene fusion, a specific molecular event seen in ∼50% of prostate carcinomas (PCas) and ∼20% of high-grade prostatic intraepithelial neoplasia (HGPIN) intermingled with adjacent PCa demonstrating identical gene fusions. We studied 84 "atypical glands suspicious for cancer (ATYP)" cases using multiplex ERG/α-methylacyl-CoA-racemase (AMACR)/high- molecular-weight cytokeratin/p63 IHC to determine how often ERG contributes to resolving an ATYP diagnosis beyond that provided by AMACR and basal markers. Final diagnoses of benign, ATYP, and cancer were rendered after review of morphology and all markers in 3, 30, and 51 cases, respectively. Of 51 cancer diagnoses, 45% and 94% were positive for ERG and AMACR, respectively. Of 30 atypical diagnoses, 10% and 67% were positive for ERG and AMACR, respectively. Of 3 benign diagnoses, none and 83% were positive for ERG and AMACR, respectively. Three ERG-positive atypical cases were classified as "HGPIN with adjacent ATYP." ERG was expressed in adjacent noncancer glands of 20% of PCas, whereas AMACR was expressed in noncancer glands in all diagnostic categories in 40% of cases. Positive ERG staining helped establish the initial ATYP diagnosis to PCa in 28% cases whose diagnoses would otherwise remain ATYP based on AMACR and basal markers. ERG positivity in small atypical glands where HGPIN diagnosis is excluded helps establish a definitive cancer diagnosis in a small proportion of additional ATYP cases. We recommend judicious use of ERG, preferably as a component of multiplex IHC, in evaluation of difficult prostate biopsies.