Plasma immunoreactive calcitonin in lung cancer

We have measured plasma calcitonin (CT) in 135 untreated eucalcemic men with lung cancer and a control/smoker population. CT levels were determined by RIA and validated by immunoextraction. Plasma immunoreactive CT moieties were purified by immunoadsorbent chromatography, treated with mercaptoethanol and urea, and characterized by gel filtration. Artifacts in human CT RIAs of cancer patient plasmas were detected by parallel plasma incubations in a salmon CT RIA system, which does not detect human CT, and by immunoprecipitation of tracer at the end of RIA incubations. Heating fresh plasmas to 65 C for 1.5 h reduced RIA artifacts without loss of CT moieties. Such characterization of hypercalcitoninemia in each of the histopathological types of lung cancer has raised some important questions about the interpretation of plasma CT RIA measurements in lung cancer. Based on inhibition of tracer-antibody binding, plasma CT seemed to be elevated in 18% (14 of 80 samples) of the basal plasma samples obtained from patients with epidermoid or anaplastic lung cancer. Unequivocal hypercalcitoninemia (heat stable, causin;. no inhibition of antibody-tracer binding in the salmon CT P As, and immunoextractable with human CT antibodies) was not found in any of the apparently hypercalcitoninemic plasmas from persons with epidermoid or anaplastic lung cancer. By contrast, unequivocal hypercalcitoninemia was found in 27% (15 of 55 samples) of the plasma samples from patients with small cell carcinoma or adenocarcinoma. Most of the immunoreactive CT recovered from small cell and adenocarcinoma lung cancer plasmas with unequivocally elevated CT levels is much larger than the CT monomer.