title: Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens.
abstract: BACKGROUND
  Gleason grading is the strongest prognostic parameter in prostate cancer. Gleason grading is categorized as Gleason ≤ 6, 3 + 4, 4 + 3, 8, and 9-10, but there is variability within these subgroups. For example, Gleason 4 components may range from 5-45% in a Gleason 3 + 4 = 7 cancer.
  
  
  OBJECTIVE
  To assess the clinical relevance of the fractions of Gleason patterns.
  
  
  METHODS
  Prostatectomy specimens from 12823 consecutive patients and of 2971 matched preoperative biopsies for which clinical data with an annual follow-up between 2005 and 2014 were available from the Martini-Klinik database.
  
  
  METHODS
  To evaluate the utility of quantitative grading, the fraction of Gleason 3, 4, and 5 patterns seen in biopsies and prostatectomies were recorded. Gleason grade fractions were compared with prostatectomy findings and prostate-specific antigen recurrence.
  
  
  CONCLUSIONS
  Our data suggest a striking utility of quantitative Gleason grading. In prostatectomy specimens, there was a continuous increase of the risk of prostate-specific antigen recurrence with increasing percentage of Gleason 4 fractions with remarkably small differences in outcome at clinically important thresholds (0% vs 5%; 40% vs 60% Gleason 4), distinguishing traditionally established prognostic groups. Also, in biopsies, the quantitative Gleason scoring identified various intermediate risk groups with respect to Gleason findings in corresponding prostatectomies. Quantitative grading may also reduce the clinical impact of interobserver variability because borderline findings such as tumors with 5%, 40%, or 60% Gleason 4 fractions and very small Gleason 5 fractions (with pivotal impact on the Gleason score) are disclaimed.
  
  
  CONCLUSIONS
  Quantitative Gleason pattern data should routinely be provided in addition to Gleason score categories, both in biopsies and in prostatectomy specimens.
  
  
  RESULTS
  Gleason score is the most important prognostic parameter in prostate cancer, but prone to interobserver variation. The results of our study show that morphological aspects that define the Gleason grade in prostate cancer represent a continuum. Quantitation of Gleason patterns provides clinically relevant information beyond the traditional Gleason grading categories ≤ 3 + 3, 3 + 4, 4 + 3, 8, 9 -1 0. Quantitative Gleason scoring can help to minimize variations between different pathologists and substantially aid in optimized therapy decision-making.
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany. Electronic address: g.sauter@uke.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Steurer
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Till Sebastian
authors.initials: TS
authors.lastname: Clauditz
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Till
authors.initials: T
authors.lastname: Krech
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Wittmer
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Lutz
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Lennartz
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Janssen
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Nayira
authors.initials: N
authors.lastname: Hakimi
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: von Petersdorff-Campen
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jacobsen
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: von Loga
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Wilczak
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Maria Christina
authors.initials: MC
authors.lastname: Tsourlakis
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Chirico
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Haese
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Heinzer
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Beyer
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Graefen
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Michl
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Salomon
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Steuber
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Lars Henrik
authors.initials: LH
authors.lastname: Budäus
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Hekeler
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Malsy-Mink
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Kutzera
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Fraune
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Cosima
authors.initials: C
authors.lastname: Göbel
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.affiliation: Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg- Eppendorf, Germany; Department of Urology, Section for translational Prostate Cancer Research, University Medical Center Hamburg-Eppendorf, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
mesh_terms: D000368:Aged; D001706:Biopsy; D018572:Disease-Free Survival; D005858:Germany; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D015588:Observer Variation; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery*; D015203:Reproducibility of Results; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Gleason score; Prognosis; Prostate cancer; Quantitative Gleason grade