To investigate the possible embryologic relation between small-cell carcinoma of the lung and medullary thyroid carcinoma, we measured plasma histaminase (an enzyme found in medullary carcinoma tissue) in 25 patients with small-cell tumors. The assays used histamine and putrescine as substrates. Thirty-two per cent of the patients by the histamine assay, and 31 per cent by the putrescine, had values greater than +2 S.D. from the mean for 63 normal persons. In contrast, among 20 patients with squamous and large-cell lung tumors, one (by the histamine assay), and two (by the putrescine) had elevated values. In four of five autopsy cases, histaminase was high in small-cell carcinoma tissue. The enzyme in plasma and in tumor behaved as classic histaminase in substrate specificity, and in response to inhibitors. The data support the proposed embryologic relation between small-cell lung carcinoma and medullary thyroid carcinoma, and further associate histaminase with some neural crest tumors. (N Engl J Med 293:1286–1290, 1975), HISTAMINASE (diamine oxidase) is consistently high in medullary thyroid carcinoma tissue,.
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