p53 mutations in human bladder cancer: Genotypic versus phenotypic patterns Journal Article


Authors: Cordon-Cardo, C.; Dalbagni, G.; Saez, G. T.; Oliva, M. R.; Zhang, Z. F.; Rosai, J.; Reuter, V. E.; Pellicer, A.
Article Title: p53 mutations in human bladder cancer: Genotypic versus phenotypic patterns
Abstract: The objective of this study was to characterize the pattern of p53 mutations in bladder cancer. The sensitivity and specificity to detect these mutations using clinical material was assessed for the following assays: immunohistochemistry, restriction‐fragment‐length polymorphism, single‐strand‐conformation polymorphism, and sequencing. Discrepancies of reported results aimed at the identification of genetic alterations in the p53 gene may be due to differences in methodology, as well as to deficient morphological evaluation of the source of tissue utilized. In order to address these critical issues, we have implemented a novel experimental design that permits analysis by molecular genetics and immunopathology techniques in any given tissue specimen, allowing morphological correlation with genotypic and phenotypic characteristics of the tissue analyzed. Forty‐two patients affected with bladder tumors in whom paired normal and tumor tissues were available were used for the present study. Nuclear immunoreactivities were observed in 26 out of 42 bladder tumors analyzed. Abnormal shifts in mobility were noted in 14 of the 42 cases in distinct exons, with one tumor revealing 3 mutations. There was a strong association between p53 nuclear over‐expression and 17p LOH, as well as p53 nuclear over‐expression and detection of mutations by SSCP and sequencing. According to receiver‐operating‐curve statistical analysis, the accuracy of detecting p53 mutations by IHC was estimated to be 90.3%. It is our conclusion that, when properly used, this is a highly sensitive and specific method with simple application using clinical material. Copyright © 1994 Wiley‐Liss, Inc., A Wiley Company
Keywords: immunohistochemistry; clinical article; controlled study; human tissue; gene mutation; mutation; comparative study; neoplasm staging; sensitivity and specificity; polymerase chain reaction; phenotype; genotype; bladder cancer; protein p53; tumor suppressor gene; antibodies, monoclonal; bladder neoplasms; genes, p53; chromosome mapping; chromosomes, human, pair 17; polymorphism, restriction fragment length; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
Journal Title: International Journal of Cancer
Volume: 56
Issue: 3
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 1994-02-01
Start Page: 347
End Page: 353
Language: English
DOI: 10.1002/ijc.2910560309
PROVIDER: scopus
PUBMED: 7906253
DOI/URL:
Notes: Source: Scopus
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  1. Guido Dalbagni
    325 Dalbagni
  2. Juan Rosai
    181 Rosai
  3. Victor Reuter
    1223 Reuter
  4. Zuo-Feng Zhang
    102 Zhang