title: Molecular Analysis of Low Grade Prostate Cancer Using a Genomic Classifier of Metastatic Potential.
abstract: We determined how frequently histological Gleason 3 + 3 = 6 tumors have the molecular characteristics of disease with metastatic potential.
  
  
  
  We analyzed prostatectomy tissue from 337 patients with Gleason 3 + 3 disease. All tissue was re-reviewed in blinded fashion by genitourinary pathologists using 2005 ISUP (International Society of Urological Pathology) Gleason grading criteria. A previously validated Decipher® metastasis signature was calculated in each case based on a locked model. To compare patient characteristics across pathological Gleason score categories we used the Fisher exact test or the ANOVA F test. The distribution of Decipher scores among different clinicopathological groups was compared with the Wilcoxon rank sum test. The association of Decipher score with adverse pathology features was examined using logistic regression models. The significance level of all statistical tests was 0.05.
  
  
  
  Of men with Gleason 3 + 3 = 6 disease only 269 (80%) had a low Decipher score with intermediate and high scores in 43 (13%) and 25 (7%), respectively. Decipher scores were significantly higher among pathological Gleason 3 + 3 = 6 specimens from cases with adverse pathological features such as extraprostatic extension, seminal vesicle involvement or positive margins (p <0.001). The median Decipher score in patients with margin negative pT2 disease was 0.23 (IQR 0.09-0.42) compared to 0.30 (IQR 0.17-0.42) in patients with pT3 disease or positive margins (p = 0.005).
  
  
  
  Using a robust and validated prognostic signature we found that a small but not insignificant proportion of histological Gleason 6 tumors harbored molecular characteristics of aggressive cancer. Molecular profiling of such tumors at diagnosis may better select patients for active surveillance at diagnosis and trigger appropriate intervention during followup.
authors: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: kleine@ccf.org.
authors: Eric A
authors: EA
authors: Klein
authors: GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: María
authors: M
authors: Santiago-Jiménez
authors: GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Kasra
authors: K
authors: Yousefi
authors: San Diego Pathology LLC, San Diego, California.
authors: Bruce A
authors: BA
authors: Robbins
authors: Department of Urology, Northwestern University, Evanston, Illinois.
authors: Edward M
authors: EM
authors: Schaeffer
authors: The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland.
authors: Bruce J
authors: BJ
authors: Trock
authors: The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland.
authors: Jeffrey
authors: J
authors: Tosoian
authors: GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Zaid
authors: Z
authors: Haddad
authors: San Diego Pathology LLC, San Diego, California.
authors: Seong
authors: S
authors: Ra
authors: Department of Urology, Mayo Clinic, Rochester, Minnesota.
authors: R Jeffrey
authors: RJ
authors: Karnes
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors: Robert B
authors: RB
authors: Jenkins
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors: John C
authors: JC
authors: Cheville
authors: Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors: Robert B
authors: RB
authors: Den
authors: Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors: Adam P
authors: AP
authors: Dicker
authors: GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors: Elai
authors: E
authors: Davicioni
authors: Division of Urology, Department of Surgery, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California; Surgery Section, Durham Veteran Affairs Medical Center, Durham, North Carolina.
authors: Stephen J
authors: SJ
authors: Freedland
authors: The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland.
authors: Ashley E
authors: AE
authors: Ross
mesh_terms: D000368:Aged; D001707:Biopsy, Needle / Q000379:methods; D015331:Cohort Studies; D023281:Genomics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D046509:Tissue Culture Techniques
keywords: genomics; neoplasm grading; neoplasm metastasis; prostatic neoplasms; watchful waiting