Original ArticlesUtility of PTEN and ERG Immunostaining for Distinguishing High-grade PIN From Intraductal Carcinoma of the Prostate on Needle BiopsyMorais, Carlos L. MD*; Han, Jeong S. MD*; Gordetsky, Jennifer MD*; Nagar, Michael S. MD†; Anderson, Ann E. MD†; Lee, Stephen MD*; Hicks, Jessica L.*; Zhou, Ming MD, PhD‡; Magi-Galluzzi, Cristina MD, PhD‡; Shah, Rajal B. MD§; Epstein, Jonathan I. MD*,∥,¶; De Marzo, Angelo M. MD, PhD*,∥,¶; Lotan, Tamara L. MD*,∥Author Information Departments of *Pathology ∥Oncology ¶Urology, Johns Hopkins Medical Institutions, Baltimore, MD †Division of Pathology, Integrated Medical Professionals, PLLC., Garden City, NY ‡Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH §Miraca Life Sciences, Irving, TX C.L.M. and J.S.H. contributed equally. Present address: Ming Zhou, Department of Pathology, New York University Medical Center, New York, NY. Conflicts of Interest and Source of Funding: Funding for this research was provided in part by the Prostate Cancer Foundation Young Investigator Award (T.L.L.), the NIH/NCI Prostate SPORE P50CA58236, and a generous gift from Mr David H. Koch (A.M.D.M.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Tamara L. Lotan, MD, Department of Pathology, Johns Hopkins Medical Institutions, 855 N. Wolfe Street, Baltimore, MD 21205 (e-mail: firstname.lastname@example.org). The American Journal of Surgical Pathology: February 2015 - Volume 39 - Issue 2 - p 169-178 doi: 10.1097/PAS.0000000000000348 Buy Metrics Abstract Intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified intraductal carcinoma, PIN, or borderline intraductal proliferations more concerning than PIN but falling short of morphologic criteria for intraductal carcinoma. Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated intraductal carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified intraductal carcinoma yet is very rare in high-grade PIN. Borderline intraductal proliferations, especially those with PTEN loss, have a high rate of carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish intraductal carcinoma from high-grade PIN in this setting. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.