title: Evaluation of MDM2, p16, and p53 staining levels as biomarkers of biochemical recurrence following salvage radiation therapy for recurrent prostate cancer.
abstract: OBJECTIVE
  The selection of appropriate candidates for salvage radiation therapy (SRT) to address a rising PSA following radical prostatectomy remains challenging. Herein, we provide the first evaluation of the ability of staining levels of the tumor based biomarkers MDM2, p16, and p53 to aid in prediction of biochemical recurrence (BCR) among men undergoing SRT for recurrent prostate cancer.
  
  
  METHODS
  We identified 152 patients who were treated with SRT between July 1987 and July 2003. Staining levels of MDM2, p16, and p53 in primary tumor samples removed during prostatectomy were detected using monoclonal antibodies and quantified by use of a computer-assisted method. Associations of staining levels with BCR were evaluated using Cox proportional hazards regression models; relative risks (RRs) and 95% confidence intervals (CIs) were estimated.
  
  
  RESULTS
  Compared to patients with low staining (≤median) as measured by percentage of cells with nuclear staining, there was no significant difference in risk of BCR for patients with high MDM2 staining (RR: 0.90, 95% CI: 0.57-1.45, P = 0.67), high p16 staining (RR: 0.88, 95% CI: 0.54-1.44, P = 0.62), or high p53 staining (RR: 1.33, 95% CI: 0.84-2.11, P = 0.23) in multivariable analysis. These results were consistent when considering alternate percentile cutpoints and alternate quantifications of biomarker staining.
  
  
  CONCLUSIONS
  Our results provide evidence that MDM2, p16, and p53 staining levels are not useful in the prediction of BCR after SRT. As such, these biomarkers are of little clinical use in the selection of appropriate candidates for SRT.
authors.affiliation: Biostatistics Unit, Mayo Clinic Florida, Jacksonville, Florida 32224, USA. heckman.michael@mayo.edu
authors.forename: Michael G
authors.initials: MG
authors.lastname: Heckman
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Parker
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Wu
authors.forename: Tracy W
authors.initials: TW
authors.lastname: Hilton
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ko
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Pisansky
authors.forename: Steven E
authors.initials: SE
authors.lastname: Schild
authors.forename: Li Yan
authors.initials: LY
authors.lastname: Khor
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Hammond
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Buskirk
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D016879:Salvage Therapy; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2