This Article Full Text Full Text (PDF) All Versions of this Article: 92/11/4394    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Long, S. H. Articles by Jensen, R. T. Search for Related Content PubMed PubMed Citation Articles by Long, S. H. Articles by Jensen, R. T. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Medline Plus Health Information Pancreatic Cancer Related Collections Endocrine Oncology

Secretin-Receptor and Secretin-Receptor-Variant Expression in Gastrinomas: Correlation with Clinical and Tumoral Features and Secretin and Calcium Provocative Test Results

Digestive Diseases Branch (S.H.L., M.J.B., T.K.P., J.S., R.T.J.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; National Eye Institute (M.T.), National Institutes of Health, Bethesda, Maryland, 20892-1804; Medizinische Klinik I (M.J.B., A.P.), Universitätsklinikum Hamburg-Eppendorf, 20256 Hamburg, Germany; and Department of Paediatrics and Adolescent Medicine (K.M.H.), Medical University of Graz, Auenbruggerplatz 30, A-8036 Graz, Austria

Address all correspondence and requests for reprints to: Dr. R. T. Jensen, National Institutes of Health, Building 10, Room 9C-103, Bethesda, Maryland 20892. E-mail: robertj{at}bdg10.niddk.nih.gov.

Context/Objectives: The diagnosis of Zollinger-Ellison syndrome requires secretin testing in 60% of patients. 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 whether the tumor density of secretin receptors or the presence of a secretin-receptor-variant, which can act as a dominant negative, is 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 Zollinger-Ellison syndrome 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 per ß-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 that variant expression modified the secretin-receptor response or accounted for negative tests.

Conclusions: Secretin-receptor and secretin-receptor-variant expressions 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 that the total secretin-receptor density is an important determinant of the secretin test response.