Utility of the ERG Immunostain in Conjunction with a PIN4 Cocktail in Classifying Atypical Glandular Lesions in Extended Prostatic Core Biopsies
Angela Wu, Allison Young, Scott Tomlins, Arul Chinnaiyan, L Priya Kunju. University of Michigan, Ann Arbor, MI
Background: The TMPRSS2:ERG gene rearrangement is present in approximately 45% of prostatic adenocarcinomas (PCa). Previously, we characterized an immunostain (IHC) utilizing a monoclonal antibody directed against ERG (EPR3864) as showing diagnostic utility for the detection of ERG rearranged PCa.
Design: Our study examined the utility of the ERG IHC in conjunction with a PIN4 cocktail in classifying atypical lesions in extended (>=12) prostatic core biopsies in a large tertiary care center over a 6 month period. All atypical lesions were immunostained with PIN4 cocktail and ERG. Lesion classification pre IHC and post IHC and IHC results were recorded.
Results: Forty four core biopsies were examined including 84% (37/44) with atypical glandular proliferations (25 atypical small acinar proliferations (ASAPs) and 12 atypical large glands); and 16% (7/44) with minute foci of PCa. After IHC, the final diagnoses were 34% (15/44) atypical glandular proliferations (12 ASAPs and 3 atypical large glands); 36% (16/44) PCa (13 minute foci of PCa and 3 PCa with pseudohyperplastic or atrophic features); and 30% (13/44) benign mimics (including partial atrophy and adenosis). Basal markers were negative (100%) and AMACR was positive (95%) in nearly all PCa. All benign mimics showed patchy positivity with basal markers and a subset (25%) were AMACR positive. ERG was positive in 50% (8/16) of all PCas including 62% (8/13) of minute foci of PCa and was negative in all benign mimics. Of all lesions classified as atypical glandular lesions after IHC, one was ERG positive and was classified as atypical small glands adjacent to high grade PIN (PINATYP). In 7% (3/44) of cores, the ERG positivity contributed directly to the diagnosis of PCa, as the foci were very small (2-3 acini). ERG was positive in glands outside the atypical foci in 2 (5%) cases; weak staining was present in a benign gland directly adjacent to a focus of PCa and strong staining was present in HGPIN glands separate from a focus of PINATYP.
Conclusions: Over 50% of the morphologically atypical lesions could be definitively resolved as PCa or benign mimics after IHC with PIN4 cocktail and ERG. ERG was positive in 50% of all PCa, confirming our previous findings, and was negative in all benign mimics. ERG is highly specific for PCa but can stain a subset of HGPIN. Therefore, when utilized in the proper context (HGPIN or PINATYP is excluded), ERG can help diagnose a subset of minute foci of PCa which would otherwise be classified as ASAPs based on morphology and PIN4 cocktail alone.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 167, Monday Afternoon