We propose to define in cells of prostatic carcinoma objective quantitative parameters of diagnostic and prognostic value measured by flow cytometry and image analysis. We will study cells, or nuclei derived therefrom, in approximately 300 patients with prostatic carcinoma and approximately 75 randomized patients with benign prostatic disease. The cell samples will be obtained primarily by thin needle aspiration biopsy, or, if necessary, from surgically removed tissues. By flow cytometry we will establish the distribution of DNA in populations of cells from cancer and benign hyperplasia. Normal prostates from autopsies will serve as controls. In representative cases the DNA determinations on Feulgen stained cells in smears by cytophotometry will be compared with flow cytometry. Our high resolution computer-based taxonomic image analysis system will select cell descriptors of value in distinguishing benign from malignant prostatic cells in smears. Further differences among subgroups of prostatic cancer cells of divergent diagnostic and prognostic value will be sought. The system also provides objective quantitation of morphologic features of cells and cell components such as cell size, nuclear size and shape, and nucleocytoplasmic ratio, etc. that has been shown capable of identifying subpopulation of seemingly similar cells. The data thus obtained will be correlated by statistical analysis with each other and with several parameters commonly used to evaluate patients with prostatic cancer: histologic grading (after Gleason), clinical staging and follow-up. While it is known that histologic grading and clinical staging provide a fair statistical assessment of prognosis, the striking differences in behavior observed among individual patients with various grades of prostatic cancer strongly suggest that these 2 parameters have only general clinical value. Preliminary evidence outlined in this application suggests that the proposed research may lead to a more accurate assessment of behavior of prostate cancer in individual patients and thus to a better choice of therapeutic options.
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