title: Long-term assessment of prostate cancer progression free survival: evaluation of pathological parameters, nuclear shape and molecular biomarkers of pathogenesis.
abstract: BACKGROUND
  Molecular pathways of proliferation, angiogenesis, neuroendocrine differentiation, apoptosis and alterations in nuclear structure of cancer epithelial cells are important in the pathogenesis of prostate cancer (PCa). Therefore, we evaluated the prognostic value of these parameters in 105 clinically localized PCa tumors with long-term follow-up after radical prostatectomy for progression-free survival (PFS).
  
  
  METHODS
  Nuclear roundness variance (NRV) was calculated for tumor nuclei using the graphic tracing DynaCELL system. Immunohistochemistry assessed expression of Ki67, PCNA (proliferation), Chromogranin A (neuroendocrine differentiation), CD31 (angiogenesis), BCL2 (apoptosis), and Her-2/neu (oncogene) in the tumors. Cox proportional hazards regression, Spearman's rank correlation, and Kaplan-Meier plots were employed to analyze the data.
  
  
  RESULTS
  Gleason score, focal vs. non-focal extra-prostatic extension, organ confined status, NRV, Her-2/neu, CD-31 and Ki67 were univariately significant predictors of PFS. NRV was the most significant prognostic indicator with the highest concordance index (0.7) for PFS. Gleason score, NRV and Her-2/neu were multivariately significant and yielded a concordance index of 0.77.
  
  
  CONCLUSIONS
  Her-2/neu oncogene and NRV were shown to be significant in the prediction of PFS. The assessment of alterations in nuclear structure using NRV proved to be the most significant factor in the prediction of PFS. Integration of image analysis-based NRV and molecular biomarkers with pathologic parameters should be considered for validation in the prediction of PFS.
authors.affiliation: James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. rveltri1@jhmi.edu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Veltri
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