Demonstration of immunoreactive calcitonin in sera and tissues of lung cancer patients.

In sera of 194 patients with lung carcinoma, calcitonin was estimated by radioimmunoassay with an antibody against human calcitonin. Increased levels of calcitonin-immunoreactive protein were found in 57% of the patients with small cell carcinoma, in 10% of the patients with squamous carcinoma and in only 2 patients with large cell carcinoma. In patients with small cell carcinoma, serial determinations of calcitonin were accomplished during therapy. Significantly decreased calcitonin levels were found in patients who responded to therapy with cytostatics and X-ray. Increased calcitonin levels were measured from 1 to 2 months before clinical symptoms of a relapse were detectable. Investigations on the biochemical nature of this calcitonin-immunoreactive protein were made on both serum of lung cancer patients and tumor tissue. Evidence for the production of calcitonin-immunoreactive protein directly by the tumor was given by immune histology and by determinations of calcitonin in tumor tissue. Three protein fractions, which were immunoreactive with anti-human calcitonin, with molecular weights of about 100,000, 48,000 and 20,000, were separated by gel filtration. The two higher molecular weight fractions were degraded to molecular weights of about 17,000 and about 3400--the molecular weight of physiological calcitonin--by incubation with sodium dodecyl sulphate under reducing conditions. These results led to the conclusion that it may be possible to characterize a tumor-specific calcitonin precursor molecule; in addition to its use in monitoring therapy it may be useful in the differential diagnosis of small cell carcinoma.