Prostate cancer is the most common male malignancy in the United States (317,100 new cases and 41,400 deaths in 1996). Serum PSA level is currently the most important tumor marker for detecting and monitoring prostate cancer. However, this marker is limited by a significant overlap in the serum PSA ranges seen with early cancers and with benign prostate disease. Moreover, a confirmed diagnosis of early prostate cancer produces additional dilemmas for the clinician and the patient, since the prevalence of this disease is much higher than its clinical expression. Recently, the applicants obtained evidence in primary prostatic tissues and in prostatic cell lines for a shift in the pattern of Asn-linked glycosylation during progression of prostate malignancies, similar to that observed in malignant melanoma and of breast and colon cancers. There is ample precedent for changes in the patterns of Asn-linked protein glycosylation with the appearance and progression of the malignant phenotype. The applicants have developed a relatively simple and sensitive method of quantitatively identifying this shift in Asn-linked glycosylation in extracts from fresh and frozen tissues, from paraffin embedded tissues, and from purified glycoproteins including PSA. This method is based on fluorophore-assisted carbohydrate electrophoresis, or FACE. The objective of this Phase I proposal is to develop a rapid and reliable assay for routine assessment of changes in patterns of asparagine-linked (Asn-linked) glycosylation in prostate cancer, so that these patterns can be used as new markers of metastatic potential.
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