Alteration of the p53 tumor suppressor gene in prostate cancer: Analytical approaches and clinical implications

Adenocarcinoma of the prostate is one of the most frequently diagnosed malignancies in Western countries. While some patients die within 1-2 years after diagnosis, other patients with 'latent' tumors will never suffer from any symptoms during their lifetime. These observations indicate the highly variable biological potential of prostate cancer and demonstrate the need for improved prognostic factors to determine the clinical prognosis of the individual patient and to guide currently available treatment options to a more aggressive (radical prostatectomy) or conservative (surveillance) therapeutical approach. Additionally recent investigations aim at the identification of patients at high risk for early tumor relapse following radical prostectomy, who should be considered as candidates for an intensified follow-up or an adjuvant therapy (hormonal ablation/radiotherapy). Alteration of the p53 tumor suppressor gene is currently the most common genetic alteration associated with human malignancies, and for a variety of tumor types such as superficial bladder cancer, p53 inactivation could be clearly identified as an independent prognostic variable to predict the biological aggressiveness of the individual rumor. With an average frequency of 25-30% former investigations have reported alterations of the p53 tumor suppressor gene as a genetic event rarely occurring in prostate cancer. However, although several questions regarding the determination of p53 alterations in prostate cancer, for example the poor correlation between immunohistochemistry and moleculargenetic analysis; remain to be clarified, recent studies strongly indicate that the determination of p53 inactivation allows the identification of a highly aggressive subgroup of prostatic tumors with decreased recurrence-free and long-term survival following radical prostatectomy. Recently suggested statistical models recognizing biological and genetic markers such as p53 in addition to classical parameters (Gleason score: preoperative PSA level, extracapsular growth) have been developed to better predict the clinical course of the individual patient. Opposite to the identification of p53 alteration as a single biological variable, the combination with other prognostically relevant parameters allows to include a larger cohort of patients into ana lysis. The introduction of new biomarkers e. g. p53, bcl-2 and the Retinoblastoma gene, into multiparametric prognostic models promises to reveal better prognostic information, possibly sufficient enough to adjust the therapeutic strategy to the biological aggressiveness of the individual tumor. However, future investigations will have to determine the reliability of genetic findings in random biopsies in comparison with moleculargenetic analysis of radical prostetectomy specimens in order to gain more experience in the validity of this technical approach to determine the individual prognosis Drier to prostatectomy.