Prostate cancer is the second leading cause of cancer deaths among men in the United States. Recent advances in diagnostic tests such as ultrasound and magnetic resonance imaging, coupled with improved biopsy techniques and serologic tests, have made possible early detection of this disease in asymptomatic men. However, early detection of this disease also creates treatment dilemmas due to lack of tests that can distinguish clinically significant tumors from latent tumors. To aid in the clinical management of prostate cancer patients, there is a need for identification of a biological marker that could be used to distinguish potentially aggressive tumors from latent tumors. We have recently identified a cytogenetic marker (i.e., trisomy 7) that is associated with the progression of human prostate cancer to advanced stages and to metastatic sites. Preliminary studies on 36 prostate specimens showed that the frequency of cells with trisomy 7 increased with increasing stages of the tumor. Furthermore, metastases showed a higher frequency of trisomy 7 cells than primary tumors. Most interestingly, in two patients with paired primary and metastatic tumors, trisomy 7 cells increased from 4-7% in the primary tumors to 42-45% in the metastatic tumor cells in the bone marrow. Therefore, the data suggests that trisomy 7 may be a common feature associated with the local and metastatic progression of human prostate cancer and serve as a novel marker for human prostate cancer progression. In this proposal, the investigator will examine the usefulness of trisomy 7, and other potential genetic markers for prostate tumor progression, e.g., aneusomy of chromosome 8 and loss of heterozygosity of genetic loci on 7q31, in predicting tumor behavior and prognosis. We will also compare the independent predictive values of these genetic markers with tumor grade, stage, and ploidy in multivariate analyses. The identification of a reliable genetic marker would allow clinicians to use different treatment strategies for patients who have different risks of cancer progression. For example, patients who have a genetic marker for progression/metastasis may be aggressively treated with chemotherapy after prostatectomy to eliminate micrometastasis and to reduce the risk of recurrence of the disease. Conversely, patients who do not have the progression markers may be spared the side effects associated with therapy.
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