HISTOPATHOLOGY, ENZYMATIC ANALYSIS AND PROGNOSIS

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A most important obstacle facing the diagnostic pathologist, chemotherapist, and radiotherapist in the evaluation of any attempt to alter the natural history of prostatic carcinoma lies in the great heterogeneity within any recognizable subgroup of patients with prostatic cancer. Currently, the most widely used predictor of prognosis is the grading system of Gleason; however, individuals whose tumors receive identical Gleason's grades may differ enormously in survival and biological behavior of their tumors. Preliminary studies have shown that measurement of extracted arginase, B iso-enzyme of N-acetyl-Beta-D-glucosaminidase, glucose-6-phosphate dehydrogenase, and BB iso-enzyme of creatine kinase from tumor complements this histopathological system for prediction of prognosis. Moreover, several of these enzymes complement one another for prediction of Gleason's grade. In a small series of patients followed for only a few years, certain of these enzymatic activities correlate better than Gleason's grade with survival. Activities of these enzymes are different in prostatic carcinoma and prostates with benign hyperplasia (BPH). Our objectives are (1) to determine if enzymatic activities in uninvolved portions of prostates from patients with prostatic carcinoma show any alterations similar to those seen in prostatic carcinoma, (2) prospectively to measure activities of these enzymes extracted from tumors of a series of patients sufficiently large to test their clinical usefulness definitively, and (3) to identify other biochemical phenotypic markers that complement histopathological data in prediction of prognosis and identification of homogeneous subgroups of patients with prostatic carcinoma. To our knowledge, this is the first human tumor for which multiple enzymatic markers appear to correlate with survival in the absence of therapy that prolongs life, although several well developed, analogous systems exist in animal models. Most therapeutic decisions that affect survival of patients with cancer are made based on data available at initial diagnosis. Consequently, it is of great importance to obtain from primary tumor as much information as possible that might be useful for the assessment of its biological potential. Despite much published work with rat hepatomas, the enclosed 6 reprints are the first demonstration that enzymatic activities in any human primary tumor may be more instructive than histological evaluation for prediction of prognosis; if confirmed in a larger study, this finding will facilitate "appropriate stratification in clinical trials."