MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

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.

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.

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).

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.

PloS one. 2016 Nov 15*** epublish ***

Okyaz Eminaga, Wei Wei, Sarah J Hawley, Heidi Auman, Lisa F Newcomb, Jeff Simko, Antonio Hurtado-Coll, Dean A Troyer, Peter R Carroll, Martin E Gleave, Daniel W Lin, Peter S Nelson, Ian M Thompson, Lawrence D True, Jesse K McKenney, Ziding Feng, Ladan Fazli, James D Brooks

Department of Urology, Stanford University, Stanford, CA, United States of America., The Department of Biostatistics, the University of Texas MD Anderson Cancer Center, Houston, TX, United States of America., Canary Foundation, Canary Center at Stanford, 3155 Porter Drive, Palo Alto, CA, United States of America., Department of Urology, University of Washington Medical Center, Seattle, WA, United States of America., Department of Pathology, University of California San Francisco, San Francisco, CA, United States of America., Department of Urologic Sciences and Vancouver Prostate Centre, Vancouver, BC, Canada., Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America., Department of Urology, University of California San Francisco, San Francisco, CA, United States of America., Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America., Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America., Department of Pathology, University of Washington Medical Center, Seattle, WA, United States of America., Department of Pathology, Cleveland Clinic, Cleveland, Ohio, United States of America.

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