Variable Content of Histaminase, L-Dopa Decarboxylase and Calcitonin in Small-Cell Carcinoma of the Lung: Biologic and Clinical Implications

To ascertain whether the content of endocrine markers is constant in small-cell carcinoma of the lung, levels of three markers of medullary thyroid carcinoma were studied in this tumor. Histaminase was increased in six of six primary tumors (three to 14,000 times), L-dopa decarboxylase in four of six (six to 30 times), and calcitonin in one of one (eight times) over levels in adjacent lung. Marker levels in mediastinal metastases reflected those in primary tumors in four of five patients. However, in four of seven, multiple hepatic metastases contained low to absent levels despite simultaneously high values in chest lesions. Immunohistochemical studies of histaminase revealed that within each primary tumor different cells contained different amounts of the enzyme. Since marker content varied between tumor cells, between primary tumors and between metastases in individual patients we conclude that circulating levels of these three markers cannot be expected necessarily to mirror tumor burden in patients with small-cell lung tumors. (N Engl J Med 299:105–110, 1978) THE high incidence of endocrine paraneoplastic syndromes with small-cell carcinoma of the lung has suggested a relation of this tumor to the APUD (A = amines, PU = amine precursor uptake, D = Laromatic amino acid decarboxylase) system of endocrine cells.^{1 2 3 4} Inherent in this concept is the possibility that levels of various hormones can serve as useful markers to monitor activity of this disease. Continued progress is being made in the therapeutic approach to the tumor, and in many patients all clinically apparent disease may be eliminated initially with radiotherapy or chemotherapy (or both). However, relapse of tumor inevitably occurs,.