High CDKN2A/p16 and Low FGFR3 Expression Predict Progressive Potential of Stage pT1 Urothelial Bladder Carcinoma

Clin Genitourin Cancer. 2018 Aug;16(4):248-256.e2. doi: 10.1016/j.clgc.2018.01.009. Epub 2018 Feb 2.


Background: A recent study on the comprehensive genomic profile of advanced urothelial bladder cancer (UBC) showed cyclin-dependent kinase inhibitor 2A (CDKN2A) and fibroblast growth factor receptor 3 (FGFR3) as the most often clinically relevant genomic alterations. Therefore, the prognostic role of FGFR3 and CDKN2A/p16 for pT1 UBC was studied.

Patients and methods: Clinical data and formalin-fixed paraffin-embedded tissues of pT1 UBC treated with an organ-preserving approach was analyzed retrospectively. Total RNA was isolated using commercial RNA extraction kits and mRNA expression of CDKN2A/p16 and FGFR3 was measured using single step reverse transcription quantitative real time polymerase chain reaction using RNA-specific TaqMan assays.

Results: Data from 296 patients (79.4% male; median age: 72 years) could be used for the final evaluation. Spearman correlation revealed a statistically significant negative correlation between mRNA expression of CDKN2A/p16 and FGFR3. There was a positive correlation between CDKN2A/p16 and G3 tumors (ρ = 0.1875; P = .0012) and associated carcinoma in situ (ρ = 0.1703, P = .0033) and a negative correlation between FGFR3 and these factors (ρ = -0.2791, P < .0001 and ρ = -0.2182, P = .0002). High CDKN2A/p16 expression (≥38.04) and low FGFR3 expression (<39.14) were statistically significantly associated with worse progression-free survival (PFS; P = .0194 and P = .0089). Multivariate Cox regression analysis could identify patients with low FGFR3 and high CDKN2A/p16 expression (log rank (LR) χ2 = 10.69; P = .0048) as well as tumor size ≥3 cm (LR χ2 = 6.03; P = .0141) as independent predictors for PFS.

Conclusion: High expression of CDKN2A/p16 and low expression of FGFR3 show a correlation with established prognostic features for non-muscle-invasive bladder cancer and can predict progression of stage pT1 UBC.

Keywords: CDKN2A; NMIBC; Prognosis; mRNA; p16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18 / genetics*
  • Disease Progression
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Neoplasm Staging
  • Progression-Free Survival
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Retrospective Studies
  • Tumor Burden
  • Up-Regulation*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology*


  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p18
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3