P53, CK20, and FGFR3 Overexpression is Associated with the Characteristics of Urothelial Cell Carcinoma of the Bladder

Asian Pac J Cancer Prev. 2023 Sep 1;24(9):3125-3131. doi: 10.31557/APJCP.2023.24.9.3125.


Objectives: The aim of this study was to investigate the association between the overexpression of tumor protein (P53), cytokeratin 20 (CK20), fibroblast growth factor receptor 3 (FGFR3), biomarkers and the grading, prognosis, heterogeneity, and relapse tendency of urothelial cell carcinomas (UCCs) of the bladder.

Methods: A cross-sectional study was conducted using 413 samples of Iranian patients diagnosed with UCC of the bladder. The tissue microarray technique was used to evaluate the patterns of tumor tissue. Two pathologists scored tissue staining using a semi-quantitative scoring system.

Results: The results showed that P53 was a predictor of a high-grade pattern (the area under the curve (AUC)=0.620) with a best cut-off value of 95.0 using the receiver operating characteristic (ROC) curve. CK20 was another predictor of a high-grade pattern (AUC=0.745) with a best cut-off value of 15. However, the overexpression of both biomarkers was not associated with a heterogeneous pattern and could not predict tumor-associated death or relapse. The heterogeneous (odds ratio (OR)=4.535, p-value=0.001) and non-papillary (OR= 6.363, p-value= 0.001) patterns were effective predictors of tumor recurrence among all baseline variables, including patient and tumor characteristics. FGFR3 was positive in all specimens and was not a valuable biomarker for differentiating patterns. None of the variables predicted tumor prognosis.

Conclusion: The study findings indicate that the intensity and percentage of cell staining for P53 and CK20 in the UCC of the bladder can aid in differentiating the grading patterns. The tendency of tumor relapse can be predicted by demonstrating heterogeneous and non-papillary patterns.

Keywords: Biomarkers; Bladder; Cancer diagnosis; Urothelial cancer; oncopathology.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Transitional Cell* / metabolism
  • Cross-Sectional Studies
  • Humans
  • Iran
  • Neoplasm Recurrence, Local / pathology
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Urinary Bladder / metabolism
  • Urinary Bladder Neoplasms* / pathology


  • Biomarkers, Tumor
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3
  • Tumor Suppressor Protein p53
  • KRT20 protein, human
  • TP53 protein, human