Expression of miRNAs and ZEB1 and ZEB2 correlates with histopathological grade in papillary urothelial tumors of the urinary bladder

Virchows Arch. 2014 Feb;464(2):213-20. doi: 10.1007/s00428-013-1518-x. Epub 2013 Dec 4.

Abstract

Histopathological grading of papillary urothelial tumors (PUTs) of the urinary bladder is subjective and poorly reproducible. We investigated the relationship between the expression of frequently deregulated microRNAs (miRNAs) as well as their target genes (ZEB1/ZEB2) and bladder cancer histopathological grade in an attempt to find a miRNA that might allow more reliable grading of PUTs. We measured the expression levels of four miRNAs (miR-145, miR-205, miR-125b, and miR-200c) in 120 formalin-fixed, paraffin-embedded bladder tumor tissue samples using real-time PCR assays. ZEB1 and ZEB2 expression was assessed in the same bladder tissues by immunohistochemistry. MiR-205 distinguished low-grade papillary urothelial carcinoma (LG) from high-grade papillary urothelial carcinoma (HG), and miR-145 distinguished HG from infiltrating carcinoma (CA) with an area under the receiver operator characteristic curve (AUC) of 0.992 and 0.997, respectively (sensitivity/specificity of 95.8/96.7 % and 100/91.7 %, respectively; p < 0.05). The expression level of miR-125b was significantly lower in LG than in PUNLMP, with an AUC value of 0.870 (93.3 % sensitivity and 84.2 % specificity; p < 0.05). ZEB1 immunoreactivity was more frequently detected in HG than in LG (57 % vs 13 %, p < 0.01) and in HG than in CA (57 % vs 17 %, p < 0.01). ZEB2 immunoreactivity was more frequent in CA than in HG (83 % vs 54 %, p < 0.05). ZEB1/ZEB2 and miRNAs expression seems to reliably distinguish between different grades of PUTs of the urinary bladder. They might well serve as useful complementary diagnostic biomarkers for grading of papillary urothelial tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers, Tumor / analysis
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / metabolism
  • Carcinoma, Papillary / pathology*
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / pathology*
  • Female
  • Homeodomain Proteins / analysis
  • Homeodomain Proteins / biosynthesis*
  • Humans
  • Immunohistochemistry
  • Male
  • MicroRNAs / analysis
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • Neoplasm Grading / methods
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Repressor Proteins / analysis
  • Repressor Proteins / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Transcription Factors / analysis
  • Transcription Factors / biosynthesis*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • Young Adult
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • MicroRNAs
  • Repressor Proteins
  • Transcription Factors
  • ZEB1 protein, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1