Development of a Highly Sensitive and Specific Carboxy-Terminal Human Pancreastatin Assay to Monitor Neuroendocrine Tumor Behavior

作者：O'Dorisio Thomas M^*; Krutzik Siegfried R; Woltering Eugene A; Lindholm Erika; Joseph Saju; Gandolfi Abby E; Wang Yi Zarn; Boudreaux J Phillip; Vinik Aaron I; Go Vay Liang W; Howe James R; Halfdanarson Thor; O'Dorisio M Sue; Mamikunian Gregg

来源：Pancreas, 2010, 39(5): 611-616.

DOI：10.1097/MPA.0b013e3181c68d7a

• chromogranins
• biomarkers
• neuroendocrine tumors
• carcinoid
• islet cell tumors
• cytoreduction
• embolization
• chemoembolization
• pancreastatin assay

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 286301 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.

• 出版日期2010-7