Development of a highly sensitive and specific carboxy-terminal human pancreastatin assay to monitor neuroendocrine tumor behavior.
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.
O'Dorisio
Thomas M
TM
Department of Internal Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA, USA. Thomas-odorisio@uiowa.edu
Krutzik
Siegfried R
SR
Woltering
Eugene A
EA
Lindholm
Erika
E
Joseph
Saju
S
Gandolfi
Abby E
AE
Wang
Yi-Zarn
YZ
Boudreaux
J Phillip
JP
Vinik
Aaron I
AI
Go
Vay Liang W
VL
Howe
James R
JR
Halfdanarson
Thor
T
O'Dorisio
M Sue
MS
Mamikunian
Gregg
G
D014408:Biomarkers, Tumor / Q000097:blood*; D053379:Chromogranin A / Q000097:blood; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood*; D010187:Pancreatic Hormones / Q000097:blood*; D011863:Radioimmunoassay; D015203:Reproducibility of Results
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D010187:Pancreatic Hormones; C050836:pancreastatin