MP61-11 SPINK1 DEFINES A MOLECULAR SUBTYPE OF PROSTATE CANCER MEN WITH MORE RAPID PROGRESSION FROM BIOCHEMICAL RECURRENCE TO DEATH IN AN AT RISK, NATURAL HISTORY COHORT

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research IV1 Apr 2015MP61-11 SPINK1 DEFINES A MOLECULAR SUBTYPE OF PROSTATE CANCER MEN WITH MORE RAPID PROGRESSION FROM BIOCHEMICAL RECURRENCE TO DEATH IN AN AT RISK, NATURAL HISTORY COHORT Michael Johnson, Ashley Ross, Mohammed Alshalalfa, Nicholas Erho, Kasra Yousefi, Voleak Choerung, Stephanie Glavaris, Helen Fedor, Misop Han, Elizabeth Humphreys, Alan Partin, Stephania Bezerra, Sheila Faraj, George Netto, Bruce Trock, Elai Davicioni, and Edward Schaeffer Michael JohnsonMichael Johnson More articles by this author , Ashley RossAshley Ross More articles by this author , Mohammed AlshalalfaMohammed Alshalalfa More articles by this author , Nicholas ErhoNicholas Erho More articles by this author , Kasra YousefiKasra Yousefi More articles by this author , Voleak ChoerungVoleak Choerung More articles by this author , Stephanie GlavarisStephanie Glavaris More articles by this author , Helen FedorHelen Fedor More articles by this author , Misop HanMisop Han More articles by this author , Elizabeth HumphreysElizabeth Humphreys More articles by this author , Alan PartinAlan Partin More articles by this author , Stephania BezerraStephania Bezerra More articles by this author , Sheila FarajSheila Faraj More articles by this author , George NettoGeorge Netto More articles by this author , Bruce TrockBruce Trock More articles by this author , Elai DavicioniElai Davicioni More articles by this author , and Edward SchaefferEdward Schaeffer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2192AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) is clinically and molecularly heterogeneous. Previous work has subtyped PCa on the basis of mutually exclusive genomic alterations in genes such as ERG, ETV1, SPINK1 or their lack thereof (i.e., ‘Triple Negative’). These studies failed to find a link between these alterations and clinical outcomes. Here we evaluate the prognosis of men with prostate cancer containing these common PCa subtypes treated by radical prostatectomy in the PSA era and then left untreated until the time of metastatic progression. METHODS Men with NCCN intermediate or high risk localized prostate cancer treated with RP at the Johns Hopkins Medical Institute (1992-2010) with at least 5 years of post-operative follow up were identified. Only men with initial undetectable PSA after surgery and who received no therapy prior to metastasis detection were included. A case-cohort design was used to randomly sample two cohorts; one enriched with metastasis from the entire cohort (n=319) and one enriched with metastasis from the patients with BCR (n=263). We analyzed Affymetrix Human Exon 1.0 ST GeneChip expression profiles from the two cohorts to perform subtype classification of patient tumors as ERG+, ETS+ (including ETV1, ETV4, ETV5, FLI1), SPINK1+ or Triple Negative (ERGγ2;/ ETSγ2;/ SPINK1γ2;). RESULTS Across the two cohorts, 36%, 12%, 9% and 43% of PCa were classified as ERG+, ETS+, SPINK1+, and Triple Negative, respectively. Univariable analysis shows that SPINK1+ tumors were more common in African Americans (OR: 1.7, 95% CI 0.7 – 4.0) but less commonly associated with positive surgical margins (OR: 0.1, 95% CI 0.0 – 0.4). In survival analyses, ERG+, ETS+ and Triple Negative patients did not show significant differences. However, in the post RP cohort in patients that developed metastasis, SPINK1+ had an HR of 3.1 (95% CI 1.4-7.1, p<0.01) for prostate cancer-specific mortality, while in the BCR cohort it SPINK1+ had an HR of 3.9 (95% CI 1.1-7.6, p<0.01). CONCLUSIONS SPINK1 overexpression is associated with faster time to PCSM in at risk men with biochemical and clinical recurrence following radical prostatectomy. ERG and ETS alterations are not prognostic for outcome. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e750 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Johnson More articles by this author Ashley Ross More articles by this author Mohammed Alshalalfa More articles by this author Nicholas Erho More articles by this author Kasra Yousefi More articles by this author Voleak Choerung More articles by this author Stephanie Glavaris More articles by this author Helen Fedor More articles by this author Misop Han More articles by this author Elizabeth Humphreys More articles by this author Alan Partin More articles by this author Stephania Bezerra More articles by this author Sheila Faraj More articles by this author George Netto More articles by this author Bruce Trock More articles by this author Elai Davicioni More articles by this author Edward Schaeffer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...