title: ERBB2 Expression as Potential Risk-Stratification for Early Cystectomy in Patients with pT1 Bladder Cancer and Concomitant Carcinoma in situ.
abstract: 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.
authors.affiliation: Department of Urology, University of Regensburg, Regensburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Breyer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Wirtz
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Bastian
authors.initials: B
authors.lastname: Keck
authors.forename: Philipp
authors.initials: P
authors.lastname: Erben
authors.forename: Maximilian C
authors.initials: MC
authors.lastname: Kriegmair
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.forename: Markus
authors.initials: M
authors.lastname: Eckstein
authors.forename: Mark
authors.initials: M
authors.lastname: Laible
authors.forename: Kornelia
authors.initials: K
authors.lastname: Schlombs
authors.forename: Sebastian
authors.initials: S
authors.lastname: Eidt
authors.forename: Stefan
authors.initials: S
authors.lastname: Denzinger
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D000368:Aged; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000601:surgery; D015653:Cystectomy; D018450:Disease Progression; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000601:surgery
chemical_list: D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human; C508053:ERBB2 protein, human