MDM2 and p53 immunoreactivity; independent predictors of stage progression in pTl bladder cancer (TCC)
Keegan PE., Griffiths TRL., Marsh C., Lunec J., Robinson MC., Neal DE.
Introduction: Although some studies have shown the independent value of p53 immunoreactivity in predicting stage progression of pT1 TCC, many others have confirmed histological grade to be the best predictor. MDM2 protein can bind to p53 protein, regulating its function; furthermore, abnormal expression of MDM2 is common in TCC. This study assessed the relative prognostic value of grade, MDM2 and p53 in newly diagnosed pT1 TCC. Patients and methods: Paraffin-embedded tumour specimens from 21 patients with pT1 disease (pT1G2 in eight and pT1G3 in 13) who subsequently progressed to muscle-invasive or metastatic disease, and 17 patients with pT1 disease (pT1G2 in 12 and pT1G3 in five) who remained progression-free despite a median follow-up of 72 months (range 44-100) were assessed by standard immunohistochemical methods using monoclonal antibodies against p53 (Do-7) and MDM2 (NCL-MDM2). Results: More than 40% p53 (P = 0.0387) and > 10% MDM2 (P < 0.001, both log-rank test) immunopositivity, but not high grade, were associated with a lower progression-free interval. In a multivariate analysis, both p53 and MDM2 percentage immunopositivity independently predicted a lower progressionfree interval (P= 0.049 and < 0.001, respectively, Cox regression analysis). Conclusion: This retrospective study showed that MDM2 immunoreactivity has independent prognostic value in addition to that of p53; a larger prospective evaluation is warranted. © 1998 British Journal of Urology.