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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.

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In the multivariate analysis, the presence of GSTM1 null genotype remained in the model (OR, 2.1) in addition to smoking and age.• Subjects with bladder tumour and GSTM1 null genotype were younger than patients without gene deletion ( P = 0.049).• Women with GSTM1 null genotype presented a higher OR than men ( P = 0.024). When stratified by smoking habit, smokers with both null genotypes showed an OR of 4.7.• The percentage of patients with G3 tumours was higher in patients with GSTT1 null genotype ( P = 0.013) and in patients with both null genotypes ( P = 0.002).• A higher percentage of infiltrating tumours was also observed in patients with both null genotypes ( P = 0.035). CONCLUSIONS• The data obtained in the present study suggest a higher risk of bladder cancer in individuals with the GSTM1 null genotype.• This risk is twofold higher when GSTM1 and GSTT1 null genotypes are both present and is also higher in smokers.• A greater predisposition for more aggressive tumours appears to exist, particularly when both null genotypes are combined.• Longer-term longitudinal studies are needed to confirm these results. KEYWORDSbladder tumour, glutathione S -transferase, GSTM1 , GSTT1 , prognosis OBJECTIVE• To estimate the prevalence and importance of GSTT1 and GSTM1 genotypes (implicated in glutathione S -transferase activity) in bladder cancer, to determine whether smoking and occupational factors influence this relationship, and to identify the value of GSTT1 and GSTM1 genotypes as prognostic factors. PATIENTS AND METHODS• A cross-sectional study was conducted with a group of patients with bladder carcinoma and a control group with benign conditions and no history of tumours. The controls were selected and paired as subjects were recruited.• Sociodemographic variables, smoking, professional occupation, histological features and the presence of GSTT1 and GSTM1 polymorphisms by multiplex PCR techniques were assessed. RESULTS• GSTM1 genotypes were investigated in 201 patients and 193 controls and GSTT1 genotypes in 190 patients and 163 controls.• In the patients group, GSTT1 null genotype was observed in 22.1% (not significant) and GSTM1 null genotype in 54.2% ( P = 0.008) (odds ratio, OR, 1.7); when considered together, 15.5% ( P < 0.05; OR, 3.5) of patients had both null genotypes.

Objective: To analyze the correlation between the genotypic and phenotypic patterns of p53 in patients with transitional cell carcinoma (TCC) of the urinary bladder. Materials and Methods: Cross-sectional study of 73 patients diagnosed with TCC. DNA was obtained from the tumor tissue to perform polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) of exons 5–9 of the p53 gene, with automatic sequencing done on any mutated samples. Immunohistochemistry (IHC) was also performed using anti-human P53 monoclonal antibody, and the diagnostic performance of this test was analyzed by a ROC curve, using the presence of p53 mutations found by PCR-SSCP as ‘gold standard’. Results: The cutoff point for defining immunopositivity was 20%. IHC had a specificity of 62.9%, and a sensitivity of 65.8%. The highest sensitivity values appeared in G3 tumors (75%) and infiltrating tumors (71.4%), and the highest specificity values were observed in G1 (77.7%) and G2 tumors (90%) and superficial tumors (66.6%). Mutations in exon 8 gave a positive result most frequently (73.7%) and were considered most relevant in terms of altering P53 function (60.9%). False negatives were documented in 28.5% of infiltrating tumors, and false positives in 33.4% of superficial tumors. Conclusions: There is a moderate correlation between p53 mutations and P53 protein overexpression, with this stronger in high-grade, infiltrating tumors, in exon 8 mutations, and when the mutation induces relevant changes in the protein structure. Although IHC is useful in routine clinical practice, the classic prognostic factors should still be considered the most important in the follow-up of these patients.