Prognostic significance of mucin expression in urothelial bladder cancer

Int J Clin Exp Pathol. 2014 Jul 15;7(8):4945-58. eCollection 2014.


Urothelial bladder cancer (UBC) is a common genitourinary malignancy, accounting for more than 160.000 deaths per year worldwide. Overexpression and aberrant glycosylation of mucins are frequent traits of many human cancers derived from epithelial cells, and are found to have prognostic significance in various carcinomas. The aim of this study was to further elucidate the features and significance of mucin expression in UBC. We investigated the relationship between mucin expression and clinicopathological characteristics in 539 cases of UBC by immunohistochemical analysis of MUC1, MUC2, MUC4, MUC5AC and MUC6 expression profiles. MUC1 stained 61.8% of the tumors and correlated with high tumor grade (P = 0.013). The expression of MUC2 and MUC6 was associated with low tumor grade (P < 0.000 and P < 0.022, respectively), and low pathologic stage (P < 0.001 and P = 0.001, respectively). MUC2 negative tumors were more frequently associated with the finding of carcinoma in situ in tumor surroundings (P = 0.019). UBC with divergent differentiation correlated with MUC1, MUC4 and MUC5AC staining. MUC4 expression was directly linked to cancer specific death (P = 0.027), while MUC2 and MUC6 showed inverse correlation to cancer-specific death (P < 0.001 and P = 0.005, respectively). Kaplan-Meier analyses showed that expression of MUC2 and MUC6 in UBC was significantly associated with better overall survival of the patients (P < 0.001, respectively). In Cox regression model, the absence of MUC6 expression emerged as independent predictor of death outcome. In conclusion, this study identifies MUC2 and MUC6 expression as markers of UBC with less aggressive behavior and useful predictors of better survival.

Keywords: Urothelial blader cancer; mucins; outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / mortality
  • Carcinoma, Transitional Cell / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mucins / analysis
  • Mucins / biosynthesis*
  • Prognosis
  • Proportional Hazards Models
  • Tissue Array Analysis
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology*


  • Biomarkers, Tumor
  • Mucins