title: DNA Ploidy as surrogate for biopsy gleason score for preoperative organ versus nonorgan-confined prostate cancer prediction.
abstract: OBJECTIVE
  Transformation of normal epithelium into cancer cells involves epigenetic and genetic changes and modifications in nuclear structure and tissue architecture. To evaluate nuclear morphometric alterations and clinicopathologic features for organ- vs nonorgan-confined prostate carcinoma (PCa) prediction.
  
  
  METHODS
  Of 557 prospectively enrolled patients, 370 had complete information and sufficient tumor area for all evaluated parameters (281 organ-confined and 89 nonorgan-confined PCa cases). Digital images of Feulgen DNA-stained nuclei were captured from biopsies using the AutoCyte imaging system, and the nuclear morphometric alterations were calculated. Logistic regression analysis with bootstrap resampling was used to determine the factors important for differentiation of the 2 groups and to generate models for organ- vs nonorgan-confined PCa prediction.
  
  
  RESULTS
  Several nuclear morphometric features were significantly altered and could differentiate organ- and nonorgan-confined disease. DNA ploidy was the most important factor among the significant nuclear morphometric features and was the second most important factor for organ- vs nonorgan-confined PCa prediction when considered with total prostate-specific antigen (PSA), complexed PSA, free/total PSA, biopsy Gleason score, and clinical stage. The combination of DNA ploidy with clinical stage, total PSA, and biopsy Gleason score showed an improvement of 1.5% in the area under the receiver operator characteristic curves compared with the combination of clinical stage, total PSA, and biopsy Gleason (73.97% vs 72.43%). The use of DNA ploidy in lieu of the biopsy Gleason score in each preoperative model evaluated resulted in equivalent or improved organ- vs nonorgan-confined PCa prediction.
  
  
  CONCLUSIONS
  The results of our study have shown that DNA ploidy can serve as a surrogate biomarker that has the potential to replace biopsy Gleason scores for organ- vs nonorgan-confined PCa prediction.
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-2101, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Isharwal
authors.forename: M Craig
authors.initials: MC
authors.lastname: Miller
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Mangold
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Humphreys
authors.forename: Alan W
authors.initials: AW
authors.lastname: Partin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Veltri
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D001707:Biopsy, Needle; D015331:Cohort Studies; D004247:DNA / Q000032:analysis / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009367:Neoplasm Staging; D011003:Ploidies; D011237:Predictive Value of Tests; D011300:Preoperative Care / Q000379:methods; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery*; D012372:ROC Curve; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D004247:DNA