Progastrin in serum from Zollinger-Ellison patients. An indicator of malignancy?

Abstract

Progastrin and all of its processing products were measured in serum from 48 patients with Zollinger-Ellison syndrome, 42 patients with duodenal ulcers, and 34 normal subjects. A processing-independent gastrin analysis and a conventional radioimmunoassay for the biologically active alpha-amidated gastrins were used. In serum from normal subjects, 87% (median; range, 27%-160%) of all progastrin products were alpha-amidated gastrins, whereas they constituted only 39% (15%-130%) in serum from patients with duodenal ulcers (p less than 0.01) and 46% (16%-100%) in serum from gastrinoma patients (p less than 0.01). A significantly lower percentage of alpha-amidated gastrin was found in patients with hepatic metastases (23%) than in patients with apparently benign tumors (54%). Chromatography of serum showed that large progastrin molecules occurred mainly in patients with malignant tumors, whereas smaller glycine-extended precursors dominated in patients with benign tumors. The results indicate that the total progastrin product reflects tumor synthesis of gastrin better than conventional measurements of alpha-amidated gastrin. Moreover, the results suggest that a low degree of processing of progastrin could serve as a predictor of a malignant clinical course at an early stage of the disease.