title: Retinoblastoma protein expression predicts response to bacillus Calmette-Guérin immunotherapy in patients with T1G3 bladder cancer.
abstract: OBJECTIVE
  Bacillus Calmette-Guérin (BCG) immunotherapy is regarded as the current treatment of choice for stage T1 grade 3 (T1G3) bladder cancer (BC), though its efficacy is limited by high recurrence and progression rate. Identification of molecular prognosticators that might be helpful in discriminating between responders and nonresponders to BCG treatment is therefore of major clinical importance; thus we focused on the cell-cycle related retinoblastoma protein (pRB), which had been already investigated in bladder cancer. The goal of our study was specifically to address whether its expression predicts the outcomes of BCG treatment for patients with T1G3 disease.
  
  
  METHODS
  To address this issue, paraffin-embedded specimens of 27 patients having undergone transurethral resection of T1G3 BC and intravesical instillations of BCG (induction + 1 year maintenance) were immunostained with pRB monoclonal antibody. Patients in whom the bladder muscle was not clearly visible, and healthy, as well as patients with TaG3 tumors or with concomitant carcinoma in situ were excluded. Mean follow-up was 60 months (range 15-135).
  
  
  RESULTS
  Thirteen tumors showed normal (1% to 50% labeling index) while 14 showed altered pRB expression, consisting of no expression (0% labeling index) in six and overexpression (>50% labeling index) in eight. Recurrence occurred in 10 (37%) patients and mean time to recurrence was 22.8 months (range 6-48). Recurrence rate was 57% in patients with altered and 15% in those with normal pRB expression, with a statistically significant difference in disease-free survival (P = 0.037). Progression occurred in five (18.5%) patients and mean time to progression was 24 months (range 6-48). Progression rate was 36% in patients with altered and 0% in patients with normal pRB expression, with a statistically significant difference in progression-free survival (P = 0.018).
  
  
  CONCLUSIONS
  In this homogeneous population of T1G3 bladder tumors, altered pRB expression predicted recurrence and progression after BCG treatment. These findings outline the potential role of pRB immunostaining in predicting T1G3 BC response to BCG immunotherapy.
authors.affiliation: Department of Urology and Renal Transplantation, University of Foggia, Foggia, Italy. luigicormio@libero.it
authors.forename: Luigi
authors.initials: L
authors.lastname: Cormio
authors.forename: Isabella
authors.initials: I
authors.lastname: Tolve
authors.forename: Pasquale
authors.initials: P
authors.lastname: Annese
authors.forename: Alberto
authors.initials: A
authors.lastname: Saracino
authors.forename: Rosanna
authors.initials: R
authors.lastname: Zamparese
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanguedolce
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Bufo
authors.forename: Michele
authors.initials: M
authors.lastname: Battaglia
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: Selvaggi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carrieri
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018572:Disease-Free Survival; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D016160:Retinoblastoma Protein