title: Quantitative apparent diffusion coefficient measurements obtained by 3-Tesla MRI are correlated with biomarkers of bladder cancer proliferative activity.
abstract: OBJECTIVE
  To investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer.
  
  
  METHODS
  Patients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied.
  
  
  RESULTS
  Muscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018).
  
  
  CONCLUSIONS
  ADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Sabina
authors.initials: S
authors.lastname: Sevcenco
authors.affiliation: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
authors.affiliation: Department of Biomedical Imaging and Image-guided therapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Lothar
authors.initials: L
authors.lastname: Ponhold
authors.affiliation: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Susani
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Harun
authors.initials: H
authors.lastname: Fajkovic
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Manuela
authors.initials: M
authors.lastname: Hiess
authors.affiliation: Department of Biomedical Imaging and Image-guided therapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Claudio
authors.initials: C
authors.lastname: Spick
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Tibor
authors.initials: T
authors.lastname: Szarvas
authors.affiliation: Department of Biomedical Imaging and Image-guided therapy, Medical University of Vienna, Vienna, Austria.
authors.forename: Pascal A T
authors.initials: PA
authors.lastname: Baltzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53