Patterns of p53 and H-ras Mutations related to Invasiveness and Differentiation of Transitional Cell Carcinoma in Human bladder

Woo, Seung Hyo; Lee, Hyung Lae; Kim, Wun Jae

Abstract

PURPOSE: To characterize the patterns of p53 & H-ras mutations related to invasiveness and differentiation of transitional cell carcinoma in human bladder.
MATERIALS AND METHODS
Tissues from 52 patients diagnosed as transitional cell carcinoma in the Chungbuk National University Hospital from 1992 to 1997 were used. Direct DNA sequencing was performed to detect the presence of mutated p53 and H-ras genes and to determine the types of mutations.
RESULTS
40.4%(21/52) and 11.5%(6/52) exhibited mutations in p53 and H-ras genes, respectively. In p53 gene, 26 mutations were detected in 21 specimens; 16 point mutations and 10 microdeletions-insertions in exon 7, 8, and 10, but not in exon 9. Three specimens showed mutations more than one, i.e., a triple point mutation, and two point mutation with microdeletions-insertions in p53 gene. ATG-->AAG point mutation at codon 243 was found most frequently(38.1%). Concerning the mutation of H-ras gene, 8 point mutations were detected from 6 specimens. Only one specimen showed triple point mutation. AGT-->AGA point mutation at codon 17 was the most frequent(50%). The mutation of H-ras was statistically correlated with differentiation but not with invasiveness, whereas the mutation of p53 was not statistically correlated with any of them. Mutation of both genes had correlations to differentiation(p=0.045).
CONCLUSIONS
From theses results, the mutation of H-ras gene might be a useful factor to expect the progression of transitional cell carcinoma. However, the mutation of p53 gene was insufficient as a prognostic factor of transitional cell carcinoma.