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

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)611-616
Number of pages6
JournalPancreas
Volume39
Issue number5
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Neuroendocrine Tumors
Chromogranin A
pancreastatin
pancreastatin-52
Amino Acids
Peptide Hormones
Antibodies
Liver
Tumor Burden
Quality Control
Radioimmunoassay
Neoplasms
Swine
Sensitivity and Specificity

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

O'Dorisio, T. M., Krutzik, S. R., Woltering, E. A., Lindholm, E., Joseph, S., Gandolfi, A. E., ... Mamikunian, G. (2010). Development of a highly sensitive and specific carboxy-terminal human pancreastatin assay to monitor neuroendocrine tumor behavior. Pancreas, 39(5), 611-616. https://doi.org/10.1097/MPA.0b013e3181c68d7a

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

In: Pancreas, Vol. 39, No. 5, 07.2010, p. 611-616.

Research output: Contribution to journalArticle

O'Dorisio, TM, Krutzik, SR, Woltering, EA, Lindholm, E, Joseph, S, Gandolfi, AE, Wang, YZ, Boudreaux, JP, Vinik, AI, Go, VLW, Howe, JR, Halfdanarson, T, O'Dorisio, MS & Mamikunian, G 2010, 'Development of a highly sensitive and specific carboxy-terminal human pancreastatin assay to monitor neuroendocrine tumor behavior', Pancreas, vol. 39, no. 5, pp. 611-616. https://doi.org/10.1097/MPA.0b013e3181c68d7a
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. / Development of a highly sensitive and specific carboxy-terminal human pancreastatin assay to monitor neuroendocrine tumor behavior. In: Pancreas. 2010 ; Vol. 39, No. 5. pp. 611-616.
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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.",
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AU - O'Dorisio, Thomas M.

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AU - Woltering, Eugene A.

AU - Lindholm, Erika

AU - Joseph, Saju

AU - Gandolfi, Abby E.

AU - Wang, Yi Zarn

AU - Boudreaux, J. Phillip

AU - Vinik, Aaron I.

AU - Go, Vay Liang W

AU - Howe, James R.

AU - Halfdanarson, Thor

AU - O'Dorisio, M. Sue

AU - Mamikunian, Gregg

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N2 - 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.

AB - 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.

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KW - chemoembolization

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KW - cytoreduction

KW - embolization

KW - islet cell tumors

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KW - pancreastatin assay

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