title: Clinical evaluation of p53 mutations in urothelial carcinoma by IHC and FASAY.
abstract: OBJECTIVE
  To assess the clinical benefit of the methods of detection of p53 mutations in human urothelial carcinoma.
  
  
  METHODS
  A total of 75 surgical specimens of urothelial carcinoma were analyzed using a yeast functional assay (FASAY) and immunohistochemistry (IHC), in combination with sequencing analysis.
  
  
  RESULTS
  Of the 75 specimens, 24 (32.0%) were positive (mutant) by FASAY and 23 (30.7%) were positive by IHC. The sequencing analysis confirmed that all 24 FASAY-positive tumors harbored mutations, and no mutations were detected in any FASAY-negative tumors. In contrast, nuclear accumulation of p53 protein was detected in 9 (17.6%) of 51 tumors with no mutation, and 10 (41.7%) of 24 tumors with mutation showed no positive staining on IHC. The mutations detected by FASAY and IHC were both associated with stage and grade, but null mutations of p53 were not associated with stage. Concerning chemosensitivity, 6 (85.7%) of 7 responders harbored p53 missense mutations in at least one allele (P = 0.01), and only 4 (57.1%) were judged positive by IHC (P = 0.13).
  
  
  CONCLUSIONS
  FASAY is more accurate than IHC in detecting the various types of p53 mutations, suggesting that a comprehensive approach for the detection of p53 mutations may be essential to elucidate their clinical significance.
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Okubo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Toda
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kakehi
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Tada
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016009:Chi-Square Distribution; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests / Q000379:methods; D009154:Mutation; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014516:Ureteral Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015003:Yeasts / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53