Antibody Based Detection of ERG Rearrangements in Prostate Core Biopsies, Including Diagnostically Challenging Cases.
Scott A Tomlins, Nallasivam Palanisamy, Khalid Suleman, Arul M Chinnaiyan, Lakshmi P Kunju. University of Michigan Medical School, Ann Arbor
Background: Fusions between the untranslated regions of androgen regulated genes and ERG occur in ∼50% of prostate cancers (PCAs) and encode a truncated ERG product. By FISH, ERG rearrangements are 100% specific for PCA or HGPIN immediately adjacent to ERG rearranged carcinoma. Previous studies using monoclonal antibodies against ERG on prostatectomy specimens confirmed exquisite assocation between ERG gene rearrangement by FISH and ERG expression by immunohistochemistry (IHC). The current aim is to evaluate ERG expression by IHC on prostate core biopsies, including those with atypical foci.
Design: Unstained levels from 90 prostate needle biopsies containing PCA, HGPIN or atypical foci requiring IHC for diagnosis (using basal cell markers and AMACR) were stained with a monoclonal antibody against ERG (clone EPR 3864, Epitomics). Staining of vessels and lymphocytes was used as positive staining control.
Results: ERG expression was confined to PCA glands, HGPIN and atypical foci, with no expression in any unequivocal benign glands from all 90 evaluated biopsies, including 17 biopsies requiring IHC to confirm benign diagnoses. ERG was expressed in PCA glands in 18 of 42 (43%) biopsies, including 8 of 25 (32%) biopsies with small foci of PCA requiring IHC for diagnosis. ERG was expressed in HGPIN in 3 of 17 (18%) biopsies. Two of 15 (13%) biopsies with atypical foci, including 1 biopsy with HGPIN with adjacent small atypical glands (PINATYP) requiring IHC for diagnosis and 1 biopsy with foci diagnosed as atypical after IHC expressed ERG.
Conclusions: 1) By IHC, ERG shows increased cancer specificity compared to AMACR, with no background staining of benign glands. 2) ERG expression in an atypical focus supports a diagnosis of PCA. 3) Unlike AMACR, which is expressed in nearly all HGPIN foci, ERG is expressed in only a subset. 4) As ERG rearrangements and ERG expression in PIN in prostatectomy specimens is invariably associated with adjacent PCA, ERG expression in isolated HGPIN on biopsy may be associated with a higher risk of PCA on subsequent biopsy. 5) Prospective studies are ongoing to determine the value of ERG expression in combination with standard IHC for diagnostically challenging biopsies and for risk stratifying men with isolated HGPIN.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 95, Monday Morning