title: Proliferative activity is the most significant predictor of recurrence in noninvasive papillary urothelial neoplasms of low malignant potential and grade 1 papillary carcinomas of the bladder.
abstract: BACKGROUND
  Recurrence of transitional cell carcinoma of the bladder cannot be predicted accurately by traditional criteria alone. This study examined the value of cell proliferative activity, morphometry, and expression of p53, c-erbB-2, and bcl-2 oncogenes in predicting recurrence of superficial papillary urothelial neoplasms of low malignant potential (LMP) and Grade 1 (G1) papillary carcinomas of the bladder.
  
  
  METHODS
  Sixty-two patients (mean age, 62 years) with newly diagnosed superficial pTa bladder tumors (19 LMP, and 43 G1) were analyzed retrospectively. All patients underwent transurethral resection (TUR). Median follow-up was 69 months. Serial sections from formalin-fixed, paraffin-embedded material at initial TUR were stained with monoclonal antibodies (MoAbs) DO7, CB11, and bcl-2-124. Cell proliferation was assessed by MIB-1 MoAb, the quantity of argyrophilic nucleolar organizer region-associated proteins (AgNORs), and mitotic count.
  
  
  RESULTS
  Of the 62 patients, 42 (67.7%) had one or more recurrences. Recurrence rates were higher in MIB-1 (P < 0.0001) and p53 immunopositive cases (P = 0.02), when the mitotic count was greater than 5 (P = 0.004), and in G1 carcinomas (P = 0.04). In univariate analysis, the disease-free period was shorter for MIB-1 (P < 0.0001) and p53 immunopositive (P = 0.0001) cases, for cases with high AgNOR quantity (P = 0.04), mitotic count greater than 5 (P = 0.01), and in G1 carcinomas (P = 0.002). In multivariate analysis, only MIB-1 immunoreactivity retained independent prognostic significance.
  
  
  CONCLUSIONS
  Despite the small cohort, the results confirm the prognostic value of cell proliferation and p53 expression in patients with bladder neoplasms. The results also indicate that MIB-1 immunopositivity is the most significant predictor of recurrence and disease-free survival in superficial LMP and G1 papillary bladder carcinomas.
authors.affiliation: Section of Pathology, Department of Biomedical Sciences and Human Oncology, University of Turin, Turin, Italy. achille.pich@unito.it
authors.forename: Achille
authors.initials: A
authors.lastname: Pich
authors.forename: Luigi
authors.initials: L
authors.lastname: Chiusa
authors.forename: Andrea
authors.initials: A
authors.lastname: Formiconi
authors.forename: Diego
authors.initials: D
authors.lastname: Galliano
authors.forename: Paola
authors.initials: P
authors.lastname: Bortolin
authors.forename: Alberto
authors.initials: A
authors.lastname: Comino
authors.forename: Roberto
authors.initials: R
authors.lastname: Navone
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear; D002291:Carcinoma, Papillary / Q000473:pathology*; D002455:Cell Division; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D034961:Antigens, Nuclear; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53