R. Oyasu et al., P53 GENE-MUTATIONS IN HUMAN UROTHELIAL CARCINOMAS - ANALYSIS BY IMMUNOHISTOCHEMISTRY AND SINGLE-STRAND CONFORMATION POLYMORPHISM, Modern pathology, 8(2), 1995, pp. 170-176
We examined 60 cases of human urothelial carcinomas (27 superficial an
d 33 deeply invasive) for the frequency of p53 gene mutations. Forty-t
wo cases were analyzed by both the immunohistochemical and the single-
strand conformation polymorphism (SSCP) methods, and the remaining 18
cases were assayed by SSCP alone. For the latter assay, exons 4 to 8 w
ere amplified by polymerase chain reaction, and the amplified nucleoti
des were analyzed for the evidence of mutations by gel electrophoresis
. When mobility shift was observed, direct nucleotide sequencing was p
erformed to determine mutation sequence. Three superficial and eight d
eeply invasive carcinomas demonstrated evidence of mutations. Mutation
s involved various codons randomly. The fact that all tumors with muta
tions of the p53 gene except for one were of high nuclear grade (grade
III) suggests that p53 mutation is associated with the progression of
bladder cancers. Our results indicate that SSCP is a sensitive screen
ing assay for detecting gene mutations. Immunohistochemical analysis i
s also a sensitive method but may yield false positive as well as fals
e negative results.