Diagnostic relevance of the amino-terminal cleavage peptide of procalcitonin (PAS-57), calcitonin and calcitonin gene-related peptide in medullary thyroid carcinoma patients

Abstract

We have identified the amino-terminal cleavage peptide of procalcitonin (PAS-57) in the plasma of normal human subjects and of medullary thyroid carcinoma (MTC) patients together with calcitonin (CT) and CT gene-related peptide (CGRP). Major components on reversed-phase high-pressure liquid chromatography had the retention times of synthetic PAS-57, CT and CGRP as well as of precursor proteins. Plasma levels of PAS-57 (290 ± 50 pgeq/ml; mean ± S.E.M.), CT (27 ± 8 pgeq/ml) and CGRP (8.4 ± 0.8 pgeq/ml) were respectively 2.3-, 1.6- and 1.5-fold higher in normal men ( n = 10) than in women ( n = 8). In response to 1 min intravenous calcium infusions (2 mg per kilogram body weight) PAS-57 and CT were increased 3.5- and 2.7-fold ( P < 0.001), respectively, but CGRP remained unchanged. In MTC patients ( n = 57) with raised levels of PAS-57 and CT, the molar ratio between PAS-57 and CT was 1.7-times higher than in normal subjects ( P < 0.01). We have found that PAS-57 is a predominant CT/CGRP gene derived product in the circulation of normal subjects and of MTC patients and a potential new MTC tumor marker.