Abstract

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• INTRODUCTION:

  Mutations in the p53 tumor suppressor gene are generally believed to be a late event in the progression of prostate cancer, and are associated with androgen-independence, increased angiogenesis, metastasis, recurrence, and a worse prognosis. In this review, we examine the current literature available on p53 mutations found in prostate cancer and focus on stages A (T1) and B (T2) of the disease. The alteration of genes involved in p53 regulation are also examined, as well as animal models that support an early role for p53 in the initiation and development of prostate cancer.

  RESULTS:

  We report here that p53 mutations occur in approximately one third of early stage prostate cancers and that expression of HPV E6 or over-expression of mdm2 contributes to loss of p53 function in an additional 25% of organ-confined disease. High levels of p53 mutation are found in normal prostate tissue of prostate cancer patients and in the precursor lesion, prostatic intraepithelial neoplasia, further implicating p53 mutation or loss as an early event in prostate tumorigenesis.

  Conclusions:

  In contrast to popular opinion, p53 mutations are a common event in early stage, organ-confined prostate cancer and although more studies are needed, the loss of p53 function through expression of viral or cellular oncoproteins also appears quite common. Evidence from animal models of prostate cancer further supports the notion that loss of p53 function plays a critical role in the development of prostate cancer.