CALCITONIN ELEVATION IN SMALL-CELL LUNG-CANCER WITHOUT ECTOPIC PRODUCTION

To determine the relative contribution of ectopic calcitonin (CT) prod uction versus nonectopic secretion of CT in patients with small cell l ung cancer (SCLC), serum and urine immunoreactive CT (iCT) levels of 8 6 different subjects were measured by radioimmunoassay (RIA) using two polyclonal antisera (Ab3b and Ab4). The subjects included 49 previous ly untreated patients with SCLC, 17 smokers, and 20 nonsmokers. Serum and urine iCT values were highest in the patients with SCLC, intermedi ate in the smokers, and lowest in the nonsmokers (p < 0.0003). Sixteen of the 49 patients with SCLC had tumor cell lines available for deter mination of CT mRNA expression by RNase protection assay (RPA) and iCT production by RIA. CT mRNA was detected in nine of 16 subjects and iC T in eight of 16. The tumor cell lines of seven patients had undetecta ble CT by both RPA and RIA, and of these, five had elevated urine or s erum iCT values compared with those of nonsmokers, and two had levels above all values in the smoker group. Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor samples detected iCT in two of four tumors from patients whose tumor cell lines had CT mRNA by RPA a nd iCT by RIA, but in none of six whose tumor cell lines had undetecta ble CT mRNA. Thus, increased iCT values in some patients with SCLC are likely due to sources other than CT production by tumor cells.