ERBB2 Expression as Potential Risk-Stratification for Early Cystectomy in Patients with pT1 Bladder Cancer and Concomitant Carcinoma in situ

Urol Int. 2017;98(3):282-289. doi: 10.1159/000453670. Epub 2016 Dec 17.


Background/Aims/Objectives: It is difficult to identify patients with a non-muscle-invasive bladder cancer (NMIBC) at stage pT1 with concomitant carcinoma in situ (Cis) who will benefit from an early cystectomy.

Methods: We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues of patients with NMIBC. Messenger ribonucleic acid (mRNA) expression of progesterone receptor (PGR), estrogen receptor (ESR1), ERBB2, and marker of proliferation Ki-67 (MKI67) was measured by single-step reverse transcription quantitative real-time polymerase chain reaction using RNA-specific TaqMan assays. Relative gene expression was determined by the normalization of 2 reference genes (CALM2, B2M) using the 40 ΔΔCT method and relative gene expression was correlated to the histopathological stage and oncological outcome.

Results: Of 302 patients with pT1 NMIBC in the initial transurethral resection of the bladder, 65 had a concomitant Cis. Elevated ERBB2 expression (>40.1) significantly correlated with progress in patients with and without concomitant Cis (p = 0.020 and p = 0.049, respectively). For the subgroup of pT1 with concomitant Cis, elevated ERBB2 expression significantly discriminated between a high-risk group of 55% progression-free survival (PFS) and a low-risk group of 90% PFS after a 5-year follow-up (p = 0.020). Cox-regression analysis revealed ERBB2 expression as the only independent prognostic factor for PFS (p = 0.0037).

Conclusions: High mRNA expression of ERBB2 can identify patients with pT1 NMIBC with concomitant Cis, who have a high risk of progression and might benefit from an early cystectomy.

MeSH terms

  • Aged
  • Carcinoma in Situ / metabolism*
  • Carcinoma in Situ / surgery
  • Cystectomy*
  • Disease Progression
  • Disease-Free Survival
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / analysis
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Sensitivity and Specificity
  • Treatment Outcome
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / surgery


  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Ki-67 Antigen
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2