Clinical evaluation of p53 mutations in urothelial carcinoma by IHC and FASAY.
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.
Watanabe
Jun
J
Department of Urology, Kyoto University Graduate School of Medicine, Japan.
Nishiyama
Hiroyuki
H
Okubo
Kazutoshi
K
Takahashi
Takeshi
T
Toda
Yoshinobu
Y
Habuchi
Tomonori
T
Kakehi
Yoshiyuki
Y
Tada
Mitsuhiro
M
Ogawa
Osamu
O
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
D016159:Tumor Suppressor Protein p53