title: Bcl-2 predicts response to neoadjuvant chemotherapy and is overexpressed in lymph node metastases of urothelial cancer of the bladder.
abstract: OBJECTIVE
  To assess whether Bcl-2, an inhibitor of the apoptotic cascade, can predict response to neoadjuvant chemotherapy in patients with urothelial cancer of the bladder (UCB).
  
  
  METHODS
  Bcl-2 expression was analyzed in 2 different tissue microarrays (TMAs). One TMA was constructed of primary tumors and their corresponding lymph node (LN) metastases from 152 patients with chemotherapy-naive UCB treated by cystectomy and pelvic lymphadenectomy (chemotherapy-naive TMA cohort). The other TMA was constructed of tumor samples obtained from 55 patients with UCB before neoadjuvant chemotherapy (transurethral resection of the bladder cancer) and after cystectomy with pelvic lymphadenectomy (residual primary tumor [ypT+], n = 38); residual LN metastases [ypN+], n = 24) (prechemotherapy/postchemotherapy TMA cohort). Bcl-2 overexpression was defined as 10% or more cancer cells showing cytoplasmic immunoreactivity.
  
  
  RESULTS
  In both TMA cohorts, Bcl-2 overexpression was significantly (P<0.05) more frequent in LN metastases than in primary tumors (chemotherapy-naive TMA group: 18/148 [12%] in primary tumors vs. 39/143 [27%] in metastases; postchemotherapy TMA: ypT+7/35 [20%] vs. ypN+11/19 [58%]). In the neoadjuvant setting, patients with Bcl-2 overexpression in transurethral resection of the bladder cancer specimens showed significantly (P = 0.04) higher ypT stages and less regression in their cystectomy specimens than did the control group, and only one-eighth (13%) had complete tumor regression (ypT0 ypN0). In survival analyses, only histopathological parameters added significant prognostic information.
  
  
  CONCLUSIONS
  Bcl-2 overexpression in chemotherapy-naive primary bladder cancer is related to poor chemotherapy response and might help to select likely nonresponders.
authors.affiliation: Department of Urology, University of Bern, Bern, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kiss
authors.affiliation: Department of Urology, University of Bern, Bern, Switzerland.
authors.forename: Veronika
authors.initials: V
authors.lastname: Skuginna
authors.affiliation: Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Achim
authors.initials: A
authors.lastname: Fleischmann
authors.affiliation: Department of Bioinformatics, University of British Columbia, Vancouver, Canada.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bell
authors.affiliation: Department of Urologic Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: Colin
authors.initials: C
authors.lastname: Collins
authors.affiliation: Department of Urology, University of Bern, Bern, Switzerland.
authors.forename: George N
authors.initials: GN
authors.lastname: Thalmann
authors.affiliation: Department of Urology, University of Bern, Bern, Switzerland; Department of Urologic Sciences, University of British Columbia, Vancouver, Canada. Electronic address: r_seiler@gmx.ch.
authors.forename: Roland
authors.initials: R
authors.lastname: Seiler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Bcl-2; Bladder cancer; Neoadjuvant chemotherapy; Response prediction