title: MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.
abstract: BACKGROUND
  The uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters.
  
  
  METHODS
  MUC1 IHC was performed on a multi-institutional tissue microarray (TMA) resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test.
  
  
  RESULTS
  The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS) (HR: 1.24, CI 1.03-1.49, P = 0.02), although not with disease specific survival (DSS, P>0.5). On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS), but was weakly associated with overall survival (OS).
  
  
  CONCLUSIONS
  In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.
authors.affiliation: Department of Urology, Stanford University, Stanford, CA, United States of America.|Department of Urology, University Hospital of Cologne, Cologne, NRW, Germany.
authors.forename: Okyaz
authors.initials: O
authors.lastname: Eminaga
authors.affiliation: The Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Canary Foundation, Canary Center at Stanford, 3155 Porter Drive, Palo Alto, CA, United States of America.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Hawley
authors.affiliation: Canary Foundation, Canary Center at Stanford, 3155 Porter Drive, Palo Alto, CA, United States of America.
authors.forename: Heidi
authors.initials: H
authors.lastname: Auman
authors.affiliation: Department of Urology, University of Washington Medical Center, Seattle, WA, United States of America.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Newcomb
authors.affiliation: Department of Pathology, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Jeff
authors.initials: J
authors.lastname: Simko
authors.affiliation: Department of Urologic Sciences and Vancouver Prostate Centre, Vancouver, BC, Canada.
authors.forename: Antonio
authors.initials: A
authors.lastname: Hurtado-Coll
authors.affiliation: Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.|Eastern Virginia Medical School, Pathology and Microbiology and Molecular Biology, Norfolk, VA, United States of America.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Troyer
authors.affiliation: Department of Urology, University of California San Francisco, San Francisco, CA, United States of America.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Carroll
authors.affiliation: Department of Urologic Sciences and Vancouver Prostate Centre, Vancouver, BC, Canada.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.affiliation: Department of Urology, University of Washington Medical Center, Seattle, WA, United States of America.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lin
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Nelson
authors.affiliation: Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.affiliation: Department of Pathology, University of Washington Medical Center, Seattle, WA, United States of America.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: True
authors.affiliation: Department of Pathology, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Jesse K
authors.initials: JK
authors.lastname: McKenney
authors.affiliation: The Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Ziding
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Urologic Sciences and Vancouver Prostate Centre, Vancouver, BC, Canada.
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.affiliation: Department of Urology, Stanford University, Stanford, CA, United States of America.
authors.forename: James D
authors.initials: JD
authors.lastname: Brooks
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D016896:Treatment Outcome
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1