Prostate cancer is the second leading cause of male cancer deaths in the USA. We are currently unable to: 1) predict accurately the malignant potential of localized prostate tumors, 2) interpret the meaning of positive biopsies after radiation therapy, 3) identify the subset of stage D1 patients with metastatic disease who will be hormonal responders, or 4) predict relapse in patients on hormonal therapy. Early diagnosis of prostate cancer currently depends on taking needle biopsies of palpably abnormal glands. This painful procedure is under-utilized for diagnosis and in monitoring response to therapy. We intend to evaluate the ability of fine-needle prostatic aspirates submitted for cytological evaluation and flow cytometric analysis of DNA histograms to: 1) aid in early diagnosis, 2) predict malignant potential, and 3) monitor patient response to therapy. Many studies have shown that the occurrence of abnormal amounts of DNA per cell (aneuploidy) correlates with tumor aggressiveness. Preliminary work suggests that successful therapeutic intervention decreases aneuploidy. However, no large prospective clinical study has been published for prostatic fine-needle aspirates examined by cytology and flow cytometry. We propose investigating several DNA histogram parameters (DNA index, extents of aneuploidy and of cycling cells, coefficient of variation) to find the most useful criteria for confirming the diagnosis of malignancy and the best correlates of tumor aggressiveness. We also intend to study the levels of functional androgen receptors (AR) in prostate cancer biopsies to determine their usefulness in predicting hormonal responsiveness and time to relapse. Receptors of steroid hormones are though to act at specific nuclar sites, enhancing transcription of tissue-specific genes. Functional AR are though to be associated with the salt-inextractable, nuclear matric cell fraction. Correlation of functional AR levels and DNA histogram findings with individual patient status should result in better understanding and treatment of this disease.
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