The Incidence of Microsatellite Instability, p53 Point Mutations and p53 Protein Expressions in Transitional Cell Carcinoma of the Bladder

Kwon, Tae Gyun; Chung, Sung Kwang; Kim, Bup Wan; Kim, Jin A; Kim, Jung Wan

Abstract

PURPROSE: The objectives of this study is to evaluate the role of microsatellite instability(MI) and p53 gene inactivation in transitional cell carcinoma(TCC) of the bladder.
MATERIALS AND METHODS
Total 31 cases of TCC patients, not treated with radiation or anticancer chemotherapy, were included in this study. Fifteen out of 31 patients were superficial and 16 were invasive TCC according to pathologic stage, while 16 were low grade and 15 were high grade TCC according to Ash grading system. The presence of MI was investigated in 3 loci of 9p site(D9S162, IFNA, D9S1747), and 6 loci of 17p site(D17S261, D17S513, D17S654, D17S695, D17S796, TP53) using a method based on the polymerase chain reaction(PCR). And the p53 point mutations were detected using polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) analysis. The p53 protein overexpression was determined by immunohistochemical stain using DO-7 primary antibody on formalin fixed, paraffin embedded tissue sections.
RESULTS
On MI analysis, altered band pattern were detected in 16 of 31 case(51.6%) in 9p region and 15 of 31 cases(48.4%) in 17p region. MI of the 9p region showed no association with tumor grade or stage. MI of the 17p site also showed no difference between superficial and invasive tumor group, but were higher in high grade(73.3%) than low grade tumor group(25.0%). On PCR-SSCP analysis, total 8 mutations were found in 6 cases(19.4%) and 4 of 8 mutations(50%) were at exon 8. On immunohistochemical staining, p53 nuclear overexpressions were found in 18 cases(58.1%) and more common in high grade and invasive tumor group(p<0.05). Fifteen out of 18 cases(83.3%) showed MI of the 9p or 17p regions.
CONCLUSIONS
These results suggest that the p16 alterations may occur in the early stage of tumorigenesis and p53 alterations are more associated with high grade/invasive tumor. And DNA mismatch repair system may play an important role in tumorigenesis of bladder tumor. MI analysis can be a useful method to detect early genetic alterations in transitional cell carcinoma of the bladder.