The association of histaminase with human cancer has been evaluated in this study by its presence at elevated levels in malignant effusion fluids. Over 400 fluid samples collected from 162 cancer patients of different primaries were analyzed in this study. Incidence of elevation of histaminase in the fluids were compared with that of three other tumor markers: carcinoembryonic antigens (CEA); β-subunit of human chorionic gonadotropin; and Reagan isoenzyme of alkaline phosphatase, all measured in the same fluids. High levels of histaminase were found in 44% (72 of 162) of all cases examined compared with 43% for carcinoembryonic antigens, 35% for β-subunit of human chorionic gonadotropin, and 23% for Regan isoenzyme. Except in lymphoma, elevations of this enzyme were found in all major types of cancer with varying degree of frequency. A high percentage of elevated histaminase was found in the effusion fluids of patients with cancers of the ovary (87%), colon (73%), and stomach (88%).

Examination of results of analyses of the four tumor markers in each individual patient reveals an immense diversity in the pattern of increase of these markers. Different patterns of elevation of these markers were observed among patients of different tumor primaries as well as patients with the same tumor primaries. In patients with cancer of the colon and stomach, the elevation of histaminase was found to correlate with the production of carcinoembryonic antigens in the majority of the cases; whereas among those with cancer of the ovary, the elevation of histaminase tended to concur with the production of β-subunit of human chorionic gonadotropin.

Results of this study also demonstrated that histaminase in the malignant effusion fluids was immunologically identical to that of the placenta; thus, this study provides the basis for using the placental histaminase as an antigen for the detection and quantitation of this enzyme by immunological methods in tumor cells and in the circulation of cancer patients. Positive immunohistochemical staining of this enzyme in tumor cells collected from effusion fluids has provided supportive evidence for the tumor origin of the enzyme in the effusion fluids. Overall results of this study therefore indicate that histaminase is associated with a wide variety of human cancers and suggest that this enzyme could be a biochemical marker for some of the cancers.

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This work was supported in part by Research Grants CA-17194, CA-12924, and CA-07190, awarded by the National Cancer Institute, Department of Health, Education, and Welfare.

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