Development of a highly sensitive and specific carboxy-terminal human pancreastatin assay to monitor neuroendocrine tumor behavior.

Abstract

OBJECTIVE:

Pancreastatin is a fragment of the chromogranin A (CgA) molecule. Existing pancreastatin assays, which depend on antibodies that cross-react in varying percents with the larger prohormone, may lack sensitivity and specificity to detect small changes in neuroendocrine tumor volume.

METHODS:

We developed a highly specific, sensitive pancreastatin assay. The antibody used recognizes the carboxyl terminal of the peptide hormone and was raised against a 17-amino acid porcine pancreastatin fragment with high homology with the carboxy-terminal amino acids 286-301 of the human CgA.

RESULTS:

Our assay measures more than 95% of circulating pancreastatin levels; has little or no cross-reactivity with CgA, even at plasma concentrations of 1000 ng/mL; and can detect pancreastatin levels of 17 pg/mL. Interassay reproducibility for the pancreastatin radioimmunoassay was determined from results of 3 quality control pools in 15 consecutive assays. Coefficients of variation for low, medium, and high pancreastatin levels were less than 20%. The sensitivity of serial pancreastatin assays to detect early liver tumor activity was demonstrated in 2 patients with slowly progressive neuroendocrine tumors and in patients undergoing surgical cytoreduction.

CONCLUSIONS:

This highly specific, sensitive pancreastatin assay can detect small changes in liver tumor progression and is up to 100-fold more sensitive and specific than CgA assays in the United States.

• Authors: Thomas M O'Dorisio, Siegfried R Krutzik, Eugene A Woltering, Erika Lindholm, Saju Joseph, Abby E Gandolfi, Yi-Zarn Wang, J Phillip Boudreaux, Aaron I Vinik, Vay Liang W Go, James R Howe, Thor Halfdanarson, M Sue O'Dorisio, Gregg Mamikunian
• Journal: Pancreas (Pancreas) Vol. 39 Issue 5 Pg. 611-6 (Jul 2010) ISSN: 1536-4828 [Electronic] United States
• PMID: 20124939 (Publication Type: Comparative Study, Evaluation Study, Journal Article)

Chemical References

• Biomarkers, Tumor
• Chromogranin A
• Pancreatic Hormones
• pancreastatin

Topics

• Biomarkers, Tumor (blood)
• Chromogranin A (blood)
• Female
• Humans
• Liver Neoplasms (blood, pathology)
• Male
• Middle Aged
• Neuroendocrine Tumors (blood)
• Pancreatic Hormones (blood)
• Radioimmunoassay
• Reproducibility of Results