Context/Objectives: The diagnosis of Zollinger-Ellison syndrome (ZES) requires secretin testing in 60%. Even with secretin the diagnosis may be difficult because variable responses occur and 6–30% have negative testing. The basis for variability or negative responses is unclear. It is unknown if the tumor density of secretin receptors or the presence of a secretin-receptor-variant, which can act as a dominant-negative, are important. The aim of this study was to investigate these possibilities.

Patients/Methods: Secretin-receptor and variant mRNA expression was determined in gastrinomas using real-time-PCR from 54 ZES patients. Results were correlated with Western blotting, secretin-receptor immunohistochemistry, with gastrin-provocative-test results and tumoral/clinical/laboratory features.

Results: Secretin-receptor mRNA was detectible in all gastrinomas but varied 132-fold with a mean of 0.89 ± 0.12 molecules/-actin. Secretin-receptor PCR results correlated closely with Western blotting (r = 0.95, P < 0.0001) and receptor-immunohistochemistry (P = 0.0015, r = 0.71). The variant was detected in all gastrinomas but levels varied 102-fold and were 72-fold lower than the total. Secretin-receptor levels correlated with variant levels, secretin, but not calcium and with tumor location, but not growth, extent or clinical responses. Variant levels did not correlate with the secretin. Detailed analysis provides no evidence variant expression modified the secretin-receptor response or accounted for negative tests.

Conclusions: Secretin-receptor and secretin-receptor-variant expression occur in all gastrinomas. Because the expression of the total but not variant correlated with the secretin results and no evidence for dominant negative activity of the variant was found, our results suggest the total-secretin-receptor density is an important determinant of the secretin test response.