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

Abstract

BackgroundThe 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.Material and MethodsMUC1 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.ResultsThe 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).ConclusionIn 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.

MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer

“…Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly overexpressed in diverse human carcinomas and contributes to hallmarks of the cancer cell, including EMT, stemness, anticancer drug resistance, epigenetic reprogramming, and immune evasion [13][14][15][16] . The upregulation of MUC1 as found in approximately 90% of PCs is associated with Gleason grades ≥7, aggressive disease and increased risk of recurrence [17][18][19] . In addition, MUC1 expression has been linked to (i) early biochemical failure and PC-related death 20 , and (ii) bone metastases in CRPC 21 .…”

Construction of a set of novel and robust gene expression signatures predicting prostate cancer recurrence

“…The Mucin 1 (MUC1) network plays a role in BCR after RP (Eminaga et al ., 2016; Lin et al ., 2017). MUC1 is a tumor‐associated antigen that has been intensively investigated (Apostolopoulos et al ., 2015; Kufe, 2009; Nath and Mukherjee, 2014).…”

“…These abnormalities are associated with angiogenesis (Papadopoulos et al ., 2001) and adverse clinical features (Eminaga et al ., 2016). MUC1 upregulation weakly correlates with shortening in disease‐free survival (DFS) and overall survival (OS) (Eminaga et al ., 2016) and associates with adverse histopathology following RP (Durrani et al ., 2015). A 3‐protein panel (AZGP1, MUC1, and p53) is related to poor prognosis in men with local PC (Severi et al ., 2014).…”

“…In PC, MUC1 expression is upregulated and aberrantly glycosylated (Arai et al, 2005;Cozzi et al, 2005;Rabiau et al, 2009). These abnormalities are associated with angiogenesis (Papadopoulos et al, 2001) and adverse clinical features (Eminaga et al, 2016). MUC1 upregulation weakly correlates with shortening in disease-free survival (DFS) and overall survival (OS) (Eminaga et al, 2016) and associates with adverse histopathology following RP (Durrani et al, 2015).…”

Androgen receptor and miR-206 regulation in prostate cancer

“…Investigators have focused on protein biomarkers such as MUC1, which has a strong correlation with Gleason scoring and androgen-independent prostate cancer (AIPC) onset. 5 However, there are limitations to nonenzymatic proteins as circulating biomarkers. In this review, we highlight the role of non-coding RNAs as potential biomarkers in androgen-dependent prostate cancer (ADPC) and AIDPC.…”