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A functional p53 protein is present in the majority of high grade transitional cell carcinoma of the bladder

par Noël, Jean Christophe ;Zlotta, Alexandre ;Bonnal, Jean-Louis;Fayt, Isabelle ;Haot, Jules ;Schulman, Claude
Référence British journal of urology, 80, SUPPL. 2, page (71)
Publication Publié, 1997

Article révisé par les pairs

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Résumé :

The p53 tumor suppression gene has been intensively studied in bladder cancer and the expression of p53 detected by immunochemistry has been correlated with clinical prognosis. The growth suppressive role of the p53 protein relies on its capacity to activate the transcription of several proteins and particularly the p21WAF1/CIP1 protein, an important inhibitor of GIG2 cyclin dependent kinases which arrests cell growth. We investigated in the present study the functional status of the p53 protein by the concomitant analysis in p21WAF1-CIP1 protein expression in transitional cell carcinoma of the bladder (TCC). p21WAF1-CIP1 protein expression was determined by immunochemistry and compared in parallel with p53 expression in 33 patients with TCC of different histological grades and stages. A cut-off value of 20% was used for p53 expression. TCCs were divided in two histological grades (low and high) lesions. In five out of the six low grade TCCs (83%), a p21WAF1-CIP1 hypcrcxprcssion was associated with the absence or minimal expression (less than 10%) of the p53 protein. In high grade lesions (n=28) invasive or not a strong immunoradioactivity for the p53 protein was observed in 24 cases (86%) whereas p21WAF1-CIP1 expression was reduced in 12 cases only (43%) (p=0.009, Fisher exact test). In contrast, in high grade lesions, in 16 cases a strong overexpression of the p21WAF1-CIP1 protein was observed along with a strong immunoreactivity for p53. Our findings suggest that p53 transcriptional activity is well preserved in low grade TCC. In contrast, in high grade TCC, despite high levels of p53 expression by immunohistochcmistry a strong p21WAF1-CIP1 nuclear immunoreactivity subsists in more than 50% of the cases. These data suggest that either a basal level of p53 functional active protein is present or that p21WAF1-CIP1 may be activated by other(s) p53 independent mechanisms. Therefore, the discrepancy between the observed expression of p53 protein and its functional status by analysis of the p21WAF1-CIP1 protein expression should be umher studied in order to increase our understanding of the aggressivity of TCC.