Fatty acid synthase, Her2/neu, and E2F1 as prognostic markers of progression in non-muscle invasive bladder cancer

Ann Diagn Pathol. 2019 Apr:39:42-52. doi: 10.1016/j.anndiagpath.2019.01.002. Epub 2019 Jan 17.

Abstract

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease which has an unpredictable risk of progression to muscle-invasive bladder cancer (MIBC). The selection of patients who may benefit from early radical intervention is a challenge. To define the useful prognostic markers for progression, we analyzed the immunohistochemical expression of fatty acid synthase (FASN), Her2/neu, and E2F1 in 60 cases of NMIBC who underwent TURBT and adjuvant intravesical bacillus-Calmette-Guérin (BCG). Their predicting role for tumor recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS) was analyzed. High FASN expression was observed in 56.7% (34/60) of NMIBC cases, and FASN expression was significantly associated with the tumor size, grade, and tumor stage (p = 0.003, p < 0.001, p < 0.0001 respectively). Positive Her2/neu was noted in 18.3% (11/60) of the cases, and its expression was significantly associated with the tumor size, histologic grade, and tumor stage (p = 0.001, p = 0.002, p = 0.011 respectively). High E2F1 expression was detected in 40% of the cases, and it was associated with tumor size, histologic grade, and tumor stage (p < 0.001 for each). Analysis of follow-up period revealed that NMIBC with high FASN, positive Her2/neu, and high E2F1 expression exhibited a potent relation with tumor progression, shorter RFS, and poor PFS. Conclusions: High FASN, Her2/neu, and E2F1 are considered as adverse prognostic factors of tumor recurrence and progression in NMIBC and these patients should be followed carefully. Therefore, we suggest that FASN, Her2/neu, and E2F1 should be considered and evaluated during the selection of the appropriate management strategy for NMIBC patients.

Keywords: E2F1; FASN; Her2/neu; Immunohistochemistry; Non-muscle-invasive bladder cancer; Prognostic markers.

MeSH terms

  • Administration, Intravesical
  • Adult
  • Aged
  • BCG Vaccine / pharmacology
  • BCG Vaccine / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Chemotherapy, Adjuvant
  • Disease Progression
  • E2F1 Transcription Factor / metabolism*
  • Fatty Acid Synthase, Type I / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism*
  • Survival Analysis
  • Treatment Outcome
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / therapy*
  • Urologic Surgical Procedures / methods*

Substances

  • BCG Vaccine
  • Biomarkers, Tumor
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • FASN protein, human
  • Fatty Acid Synthase, Type I
  • ERBB2 protein, human
  • Receptor, ErbB-2