DNA STUDIES &P53 GENE ABNORMALITIES IN PROSTATE CANCER

Project: Research project

Description

The number of patients diagnosed with prostate cancer (CaP) has
increased 63% in the last seven years. Over the same time period, the
number of deaths has risen from 24,000 to 32,000 cases a year. With
the aging of the American male population and the increased use of
screening for CaP, these figures can only be expected to rise over the
coming years. Although increased numbers of patients are currently
being diagnosed with localized CaP, the malignant potential of an
individual tumor cannot be accurately determined with present
methodology. Without definition or identification of the malignant
potential of the tumor, clinical investigators are unable to
distinguish the cancers that will remain dormant from those that will
progress and compete as a cause of mortality. For patients who require
therapy, current knowledge is also lacking to allow clinicians to
predict whether their tumor will respond to radiation therapy. If an
accurate marker of tumors malignant potential were found, patients
could be offered a more rational approach to therapy that, in many
cases, would mean observation alone. Presently, two markers show promise in both these areas, namely tumor
ploidy and mutation in the p53 gene. These markers have not yet been
evaluated in a large, multi-institutional study. This proposal will
study ploidy and p53 in patients with CaP who are entered on an ongoing
clinical trial (INT-0086/SWOG-8794). Eligible patients will have been
found to be margin positive after radical prostatectomy and thus have
a high likelihood of disease progression. In this trial, patients are
randomized to observation or adjuvant radiation therapy. The usefulness
of these markers will then be evaluated utilizing specimens of 558
patients from this large multi-institutional trial. Specific aims of this proposal include the following: 1) to evaluate
the clinical usefulness of DNA ploidy of a prostate biopsies; 2) to
determine whether the ploidy of the positive margins predicts clinical
outcome; 3) to determine whether ploidy is a stronger predictor of
outcome than whether the patient receives adjuvant radiation therapy;
4) to determine whether the p53 status of the tumor is an accurate
predictor of malignant potential and response to radiation therapy; and
5) to evaluate whether determining the ploidy and p53 status of the
tumor gives additive information. Determination of the usefulness of
these markers in CaP may be an initial step in the rationalization and
individualization of treatment of patients with localized CaP.
StatusFinished
Effective start/end date7/1/936/30/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

Fingerprint

p53 Genes
Prostatic Neoplasms
Ploidies
DNA
Radiotherapy
Neoplasms
Observation
Tumor Biomarkers
Prostatectomy
Disease Progression
Prostate
Research Personnel
Biopsy
Mutation
Mortality
Therapeutics

ASJC

  • Medicine(all)