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Prognostic implications of p53 gene mutations in bladder tumors
J G Lorenzo-Romero1, A S Salinas-Sánchez, J M Giménez-Bachs
1Urology Service, Hospital and University Complex of Albacete and the Department of Genetics, Faculty of Medicine, University of Castilla-La Mancha, Albacete, Spain.
Purpose:
Alterations in the p53 gene related to neoplastic progression were studied in tumor tissue samples from patients with transitional cell carcinoma and correlated with classic staging parameters. On this basis, biological characterization of the tumor was performed to establish subgroups of patients at high risk and those with a more favorable prognosis.
Materials And Methods:
This observational, analytical and cross-sectional study included 115 patients divided into 4 homogeneous groups of 1-control, 2-primary superficial transitional cell carcinoma, 3-recurrent superficial transitional cell carcinoma, and 4-infiltrative transitional cell carcinoma. DNA was obtained from tumor tissue samples and polymerase chain reaction-single strand conformational polymorphism analysis was performed on exons 5 to 9 of the p53 gene. Samples showing mutations were submitted to automatic sequencing. Statistics included bivariate analysis and logistic regression.
Results:
Of the tumors the 63.8% were superficial and 37.2% were infiltrative transitional cell carcinoma. Of the infiltrative tumors 23.5% (8 of 34) resulted from recurrent transitional cell carcinoma. Mutations were found in samples from 46.8% of patients, all with bladder tumors. There was a trend toward increasing appearance of mutations as the size of the tumor, number of tumor implants, degree of dedifferentiation and stage of local infiltration increased. The presence of mutations in p53 was 2.5 times greater in infiltrative tumors than in low stage and 4.3 times greater in moderate to high grade than in low grade tumors. All mutations found were point mutations and 79.25% provoked severe alterations in protein structure.
Conclusions:
Mutations in the p53 gene are mainly point mutations that aggregate in hot spots, and provoke genetic instability and substantial changes that alter p53 function, implying a trend to tumor progression and dissemination (with a greater proportion of mutations in high stage high grade tumors). Since a large percentage of bladder tumors are under staged, analysis of p53 gene mutations could be useful as a factor for prognosis and therapeutic decisions.