MP1-17 PTEN STATUS DETERMINATION IN PROSTATE CANCER: COMPARISON OF IHC AND FISH IN A LARGE MULTI-CENTER COHORT

Abstract

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 2015MP1-17 PTEN STATUS DETERMINATION IN PROSTATE CANCER: COMPARISON OF IHC AND FISH IN A LARGE MULTI-CENTER COHORT Tamara L. Lotan, Carlos L. Morais, Wei Wei, Tamara Jamaspishvili, Ziding Feng, Jesse McKenney, Jeff Simko, Dean Troyer, Lawrence True, James D. Brooks, Jeremy Squire, and CAnary Pathology Team Investigating Tissue Biomarkers (CAPIT) Tamara L. LotanTamara L. Lotan More articles by this author , Carlos L. MoraisCarlos L. Morais More articles by this author , Wei WeiWei Wei More articles by this author , Tamara JamaspishviliTamara Jamaspishvili More articles by this author , Ziding FengZiding Feng More articles by this author , Jesse McKenneyJesse McKenney More articles by this author , Jeff SimkoJeff Simko More articles by this author , Dean TroyerDean Troyer More articles by this author , Lawrence TrueLawrence True More articles by this author , James D. BrooksJames D. Brooks More articles by this author , Jeremy SquireJeremy Squire More articles by this author , and CAnary Pathology Team Investigating Tissue Biomarkers (CAPIT)CAnary Pathology Team Investigating Tissue Biomarkers (CAPIT) More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.180AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES PTEN loss is a promising prognostic and potentially predictive biomarker in prostate cancer. Because PTEN loss in prostate cancer occurs most commonly via gene deletion, we developed and validated an inexpensive immunohistochemical (IHC) assay to detect PTEN protein loss. Here, we studied the sensitivity and specificity of this assay relative to fluorescence in situ hybridization (FISH) for detection of PTEN gene deletion in prostate cancer. METHODS 1275 primary prostate tumors from the Canary Retrospective Prostate Cancer Tissue Microarray (TMA) cohort were analyzed for PTEN loss by IHC. PTEN IHC was performed by autostaining on the Ventana Discovery Ultra platform using a rabbit monoclonal antibody (Cell Signaling, clone D4.3) and scored by two independent reviewers with very good agreement (96.4% agreement over 2783 spots; κ = 0.905; 95% CI=0.887-0.923). FISH was previously performed in the same cohort using a four color probe set (CymogenDx) yielding measurable results for 612 tumors. RESULTS By IHC, 8% (108/1275) of tumors had homogeneous PTEN loss in all sampled tumor glands, 12% (150/1275) had heterogeneous PTEN loss in a subset of sampled tumor glands, 66% (837/1275) had intact PTEN and 14% (180/1275) had ambiguous or missing immunostaining results. 551 tumors had both IHC and FISH data available for comparison. Intact PTEN immunostaining was 91% specific for absence of PTEN gene deletion by FISH, with 413/454 tumors with 2 copies of PTEN showing intact PTEN IHC. PTEN IHC loss was 98% sensitive for homozygous PTEN deletion by FISH, with homogeneous or heterogeneous PTEN protein loss in 48/49 homozygous tumors. PTEN IHC was 62% sensitive for detection of hemizygous PTEN deletion by FISH, with homogeneous or heterogeneous PTEN protein loss in 30/48 tumors with hemizygous deletion. Other inactivating mutations of PTEN (not detectable by FISH) may lead to PTEN protein loss in tumors with normal or hemizygous PTEN copy number. CONCLUSIONS Our validated and automated PTEN immunostaining protocol is a simple and relatively inexpensive test that is 91% specific and 98% sensitive for detection of homozygous PTEN gene deletions in a large multi-center study of prostate cancer. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e7-e8 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tamara L. Lotan More articles by this author Carlos L. Morais More articles by this author Wei Wei More articles by this author Tamara Jamaspishvili More articles by this author Ziding Feng More articles by this author Jesse McKenney More articles by this author Jeff Simko More articles by this author Dean Troyer More articles by this author Lawrence True More articles by this author James D. Brooks More articles by this author Jeremy Squire More articles by this author CAnary Pathology Team Investigating Tissue Biomarkers (CAPIT) More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...