title: Inverted urothelial papilloma: is ploidy, MIB-1 proliferative activity, or p53 protein accumulation predictive of urothelial carcinoma?
abstract: BACKGROUND
  Inverted urothelial papilloma is an unusual neoplasm of the urinary tract. Although the association between inverted urothelial papilloma and urothelial carcinoma is not entirely clear, many studies indicate that patients with inverted papilloma are at increased risk for the development of urothelial carcinoma. In addition, aneuploid inverted papillomas have been associated with the subsequent development of urothelial carcinoma. The objective of this study was to determine whether ploidy, MIB-1 proliferative activity, or p53 protein staining in inverted papilloma were predictive of urothelial carcinoma.
  
  
  METHODS
  Fifty-one cases of inverted papilloma were retrieved from the Tissue Registry of the Mayo Clinic. Clinical records were reviewed for patient age, length of follow-up, and history of urothelial carcinoma (defined as carcinoma prior to, concurrent with, or subsequent to the diagnosis of inverted papilloma). DNA ploidy analysis was determined using Feulgen stained sections from paraffin embedded tissues using an image analysis system. Quantitation of MIB-1 proliferative activity and p53 immunostaining was determined similarly using immunoperoxidase stained sections from paraffin embedded tissues.
  
  
  RESULTS
  The mean age at diagnosis of inverted papilloma was 63.9 years (range, 37-87 years), and there were 39 men and 12 women. Patients were followed for a mean of 56.5 months (range, 1-252 months). Tumors ranged in size from 0.2 to 4.3 cm (mean, 0.9 cm). Eight patients (15.7%) had a prior, concurrent, or subsequent noninvasive World Health Organization and International Society of Urologic Pathology (WHO/ISUP) papillary neoplasm of low malignant potential or papillary carcinoma of low grade (formerly WHO Grade 1 or 2 papillary urothelial carcinoma). Inverted papillomas in patients with a history of urothelial carcinoma were all diploid and had a mean MIB-1 activity of 6.3% (range, 0.04-24.8%) and mean p53 protein staining of 12.6% (range, 0.5-24.9%). These inverted papillomas ranged in size from 0.3 to 1.0 cm (mean, 0.5 cm). Inverted papillomas in patients without a history of urothelial carcinoma were aneuploid in 6 cases (14.3%) and diploid in the remaining cases. These inverted papillomas had a mean MIB-1 activity of 1.6% (range, 0.06-9.0%) and mean p53 protein staining of 9.7% (range, 0.05-38.0%). Tumor size ranged from 0.2 to 4.3 cm (mean, 1.0 cm). There were no statistically significant differences in MIB-1 activity, p53 protein staining, ploidy, and morphologic features between inverted papillomas in patients with and without a history of urothelial carcinoma.
  
  
  CONCLUSIONS
  Ploidy, MIB-1 proliferative activity, and p53 immunostaining in inverted urothelial papilloma were not useful in identifying patients who had a history of urothelial carcinoma.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Cheville
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.forename: T J
authors.initials: TJ
authors.lastname: Sebo
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: D
authors.initials: D
authors.lastname: Riehle
authors.forename: C M
authors.initials: CM
authors.lastname: Lohse
authors.forename: V
authors.initials: V
authors.lastname: Shane
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004396:Coloring Agents; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis*; D004171:Diploidy; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D007091:Image Processing, Computer-Assisted; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D018308:Papilloma, Inverted / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016612:Paraffin Embedding; D011003:Ploidies; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D014571:Urologic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D034961:Antigens, Nuclear; D001324:Autoantigens; D014408:Biomarkers, Tumor; D004396:Coloring Agents; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53