MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden

Abstract

Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score X7 and MUC-1 deviating from the normal had a 17 (RR ¼ 17.1 95% confidence interval ¼ 2.3 -128) times higher risk to die in prostate cancer compared with men with Gleason score o7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

Assessing Expression of MUC1 and ZAG Protein Biomarkers in Prostate Biopsies Improves Prediction of Adverse Pathology Following Radical Prostatectomy

“…High risk cancers generally had higher serum PSA concentrations, higher proportions of cores with cancer, higher median cancer length per core, and more adverse Gleason variables than not high-risk cancers ( Table 2). MUC1 expression was more frequent and ZAG staining less frequent in the biopsies from high-risk cancers compared with those not high-risk, consistent with the known biology of these proteins in prostate cancer [10,12,[30][31][32][33]. In those biopsies with >40% MUC1 staining, the associated RPx specimens had a much higher percentage of pattern 4 histopathology than in those without biopsy MUC1 expression (median 70% versus 20%, p<0.001, Wilcoxon rank-sum test).…”

“…Prior studies of RPx tissue have shown positive MUC1 or ZAG expression to be predictive of PSA failure and/or metastases, [10,12,[30][31][32][33] but no studies have investigated these markers in prostate biopsies, although Gunia et al showed that MUC1 expression in transurethral resection specimens ("incidental prostate cancers") predicted adverse pathology following subsequent radical prostatectomy [41]. The failure of our study to document a predictive capacity of MUC1 expression is most likely related to the small sample size (as relatively few biopsies stained MUC1 positive, the study lacked power to assess this biomarker), although it is also possible that its expression in biopsies is not strongly related to RPx pathology.…”

Determining Prostate Cancer-Specific Death through Quantification of Stromogenic Carcinoma Area in Prostatectomy Specimens

“…Few studies that have analyzed prediction of PCa-specific death, 39,46 -51 and even fewer have attempted to identify biomarkers of PCa-specific death. [52][53][54][55] The study reported here was possible because of our unique resources, including a large tissue bank and database with extensive follow-up clinical data for Ͼ15 years. Unlike most other cancers, PCa-specific death continues up to the 20th year of follow-up.…”

Fascin Regulates Prostate Cancer Cell Invasion and Is Associated with Metastasis and Biochemical Failure in Prostate Cancer

“…Theoretical intensity levels ranged from 0 to 255 chromogen intensity units. The correlation coefficient for the ASCIS II was r 2 = 0.973, and the reproducibility for the system was previously tested and confirmed by scoring several tissue microarrays on separate occasions and in previous publications (33,34).…”