Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 11, November, p. 1319–1324

doi: 10.17219/acem/126290

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Chromogranin A assessment in patients with neuroendocrine neoplasm of the small bowel and carcinoid syndrome treated with somatostatin analogues

Paweł Gut1,A,B,C,D, Agata Czarnywojtek2,C,E,F, Marek Ruchała1,E,F

1 Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poland

2 Department of Pharmacology, Poznan University of Medical Sciences, Poland

Abstract

Background. Chromogranin A (CgA) is one of the non-specific markers measured in the biochemical diagnostics of neuroendocrine neoplasms (NENs).
Objectives. To analyze the CgA levels of patients with carcinoid syndrome who are being treated with somatostatin analogues (SSAs), depending on the histologic maturity of the neoplasm, the degree of liver involvement and the stage of the disease.
Material and Methods. The study group comprised of 41 patients, including 29 women (70.7%) and 12 men (29.3%). All of the patients had undergone surgical removal of the primary site. Hepatic metastases were found in all patients and they all were treated with SSAs. Chromogranin A concentration was determined using the enzyme-linked immunosorbent assay (ELISA).
Results. Among the patients with grade 1 tumors, the mean CgA value was 298.83 ng/mL, whereas in the group with grade 2 tumors, the CgA value was 1498.44 ng/mL, which was a statistically significant difference (p < 0.001). In the group of patients with 10% liver involvement, the mean CgA value was 394.44 ng/mL, whereas in the group of patients with 25% liver involvement, this value was 1770.63 ng/mL, demonstrating significantly higher values (p < 0.001). Among the patients with a progressing disease, the mean CgA concentration value was 1620.78 ng/mL, whereas in the group of patients with a stable disease, these were considerably lower, amounting to 230.36 ng/mL (p < 0.001).
Conclusion. Assessing CgA level in patients with carcinoid syndrome is helpful in the diagnostics and monitoring of treatment because CgA values depend on the tumor grade and the severity of the disease.

Key words

chromogranin A, carcinoid syndrome, somatostatin analogues

References (38)

  1. Nehar D, Lombard Bohas C, Olivieri S. Interest of chromogranin A for diagnosis and follow-up of endocrine tumors. Clin Endocrinol (Oxf). 2004;60(5):644–652.
  2. Glinicki P, Jeske W. Chromogranin A (CgA): Characteristics of available research methods and conditions that may affect the results obtained [in Polish]. Endokrynol Pol. 2009;60(5):415–419.
  3. Glinicki P, Jeske W. Chromogranin A (CgA): The influence of various factors in vivo and in vitro and existing disorders on its concentration in blood. Endokrynol Pol. 2010;61(4):384–387.
  4. Nobels FR, Kwekkeboom DJ, Coopmans W, et al. Chromogranin A as serum marker for neuroendocrine neoplasia: Comparison with neuron-specific enolase and the alpha subunit of glycoprotein hormones. J Clin Endocrinol Metab. 1997;82(8):2622–2628.
  5. Bilek R, Safarik L, Ciprova V, Vlcek P, Lisá L. Chromogranin A, a member of neuroendocrine secretory proteins, as a selective marker for laboratory diagnosis of pheochromocytoma. Physiol Res. 2008;57(Suppl 1):S171–S179.
  6. O’Connor DT, Pandian MR, Carlton E, Cervenka JH, Hslao RJ. Rapid radioimmunoassay of circulating chromogranin A: In vitro stability, exploration of the neuroendocrine character of neoplasia, and assessment of the effects of organ failure. Clin Chem. 1989;35(8):1631–1637.
  7. Waldum HL, Syversen U. Serum chromogranin A in the control of patients on long-term treatment with inhibitors of acid secretion. Eur J Clin Invest. 2001;31(9):741–743.
  8. Gut P, Czarnywojtek A, Fischbach J, et al. Chromogranin A – unspecific neuroendocrine marker: Clinical utility and potential diagnostic pitfalls. Arch Med Sci. 2016;12(1):1–9.
  9. Glinicki P, Kapuścińska R, Jeske W. The differences in chromogranin A concentrations measured in serum and in plasma by IRMA and ELISA methods. Endokrynol Pol. 2010;61(4):346–350.
  10. Kos-Kudła B. Treatment of neuroendocrine tumors: New recommendations based on the CLARINET study. Contemp Oncol (Pozn). 2015;19(5):345–349.
  11. Kunikowska J, Królicki L, Sowa-Staszczak A, Pawlak D, Hubalewska-Dydejczyk A, Mikołajczak R. Nephrotoxicity after PRRT: Still a serious clinical problem? Renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATATE and 90Y/177Lu-DOTATATE. Endokrynol Pol. 2013;64(1):13–20.
  12. Kos-Kudła B, Bolanowski M, Handkiewicz-Junak D, Jarząb B. Diagnostic and therapeutic guidelines for gastrointestinal neuroendocrine tumors (recommended by the Polish Network of Neuroendocrine Tumors). Endokrynol Pol. 2008;59(1):41–56.
  13. Foltyn W, Zajęcki W, Marek B, et al. The value of the Ki-67 proliferation marker as a prognostic factor in gastroenteropancreatic neuroendocrine tumours. Endokrynol Pol. 2012;63(5):362–366.
  14. Fischbach J, Gut P, Matysiak-Grześ M, et al. Combined octreotide and peptide receptor radionuclide therapy ((90)Y-DOTA-TATE) in case of malignant insulinoma. Neuro Endocrinol Lett. 2012;33(3):273–278.
  15. Stridsberg M, Eriksson B, Oberg K, Janson ET. A comparison between three commercial kits for chromogranin A measurenents. J Endocrinol. 2003;177(2):337–341.
  16. Zatelli MC, Torta M, Leon A, et al; Italian CromaNet Working Group. Chromogranin A as a marker of neuroendocrine neoplasia: An Italian Multicenter Study. Endocr Relat Cancer. 2007;14(2):473–482.
  17. Donica H, Malecha-Jędraszek A, Strosławska E, Burska A, Szubstarski F. Significance of plasma chromogranin A determination in neuroendocrine tumour (NET) diagnosis. Folia Histochem Cytobiol. 2010;48(4):603–610.
  18. Rossi RE, Garcia-Hernandez J, Meyer T, et al. Chromogranin A as a predictor of radiological disease progression in neuroendocrine tumours. Ann Transl Med. 2015;3(9):118.
  19. Cheng Y, Sun Z, Bai C, et al. Serum chromogranin A levels for the diagnosis and follow-up of well-differentiated non-functioning neuroendocrine tumors. Tumour Biol. 2016;37(3):2863–2869.
  20. Ardill JE, Armstrong L, Smye M, Doherty R, McCance DR, Johnston BT. Neuroendocrine tumours of the small bowel: Interpretation of raised circulating chromogranin A, urinary 5 hydroxy indole acetic acid and circulating neurokinin A. QJM. 2016;109(2):111–115.
  21. Tang C, Gong L, Zou W, et al. Multivariate analysis of metastasis-related risk factors for patients with gastroenteropancreatic neuroendocrine tumors based on clinicopathological and endoscopic features. Oncol Rep. 2016;36(6):3343–3352.
  22. Allen KR, Degg TJ, Anthoney DA, Fitzroy-Smith D. Monitoring the treatment of carcinoid disease using blood serotonin and plasma 5-hydroxyindoleacetic acid: Three case examples. Ann Clin Biochem. 2007;44(Pt 3):300–307.
  23. Raoof M, Jutric Z, Melstrom LG, et al. Prognostic significance of chromogranin A in small pancreatic neuroendocrine tumors. Surgery. 2018;165(4):760–766.
  24. Jun E, Kim SC, Song KB, et al. Diagnostic value of chromogranin A in pancreatic neuroendocrine tumors depends on tumor size: A prospective observational study from a single institute. Surgery. 2017;162(1):120–130.
  25. Rossi RE, Ciafardini C, Sciola V, Conte D, Massironi S. Chromogranin A in the follow-up of gastroenteropancreatic neuroendocrine neoplasms: Is it really game over? A systematic review and meta-analysis. Pancreas. 2018;47(10):1249–1255.
  26. Hofland J, Zandee WT, de Herder WW. Role of biomarker tests for diagnosis of neuroendocrine tumours. Nat Rev Endocrinol. 2018;14(11):656–669.
  27. Lyubimova NV, Churikova TK, Kushlinskii NE. Chromogranin as a biochemical marker of neuroendocrine tumors. Bull Exp Biol Med. 2016;160(5):702–704.
  28. Di Giacinto P, Rota F, Rizza L, et al. Chromogranin A: From laboratory to clinical aspects of patients with neuroendocrine tumors. Int J Endocrinol. 2018;2018:8126087.
  29. Oberg K, Modlin IM, De Herder W, et al. Consensus on biomarkers for neuroendocrine tumour disease. Lancet Oncol. 2015;16(9):435–446.
  30. Modlin IM, Oberg K, Taylor A, Drozdov I, Bodei L, Kidd M. Neuroendocrine tumor biomarkers: Current status and perspectives. Neuroendocrinology. 2014;100(4):265–277.
  31. Genç CG, Jilesen APJ, Nieveen van Dijkum EJM, et al. Measurement of circulating transcript levels (NETest) to detect disease recurrence and improve follow-up after curative surgical resection of well-differentiated pancreatic neuroendocrine tumors. J Surg Oncol. 2018;118(1):37–48.
  32. Modlin IM, Kidd M, Malczewska A, et al. The NETest: The clinical utility of multigene blood analysis in the diagnosis and management of neuroendocrine tumors. Endocrinol Metab Clin North Am. 2018;47(3):485–504.
  33. Malczewska A, Bodei L, Kidd M, Modlin IM. Blood mRNA measurement (NETest) for neuroendocrine tumor diagnosis of image-negative liver metastatic disease. J Clin Endocrinol Metab. 2019;104(3):867–872.
  34. Corsello A, Di Filippo L, Massironi S, et al. Vasostatin-1: A novel circulating biomarker for ileal and pancreatic neuroendocrine neoplasms. PLoS One. 2018;13(5):e0196858. doi:10.1371/journal.pone.0196858
  35. Kruljac I, Vurnek I, Maasberg S, et al. A score derived from routine biochemical parameters increases the diagnostic accuracy of chromogranin A in detecting patients with neuroendocrine neoplasms. Endocrine. 2018;60(3):395–406. doi:10.1007/s12020-018-1592-6
  36. Tseng CM, Cheng TY, Chen TB, et al. Low accuracy of chromogranin A for diagnosing early-stage pancreatic neuroendocrine tumors. Oncol Lett. 2018;15(6):8951–8958. doi:10.3892/ol.2018.8472
  37. Caplin ME, Pavel M, Ćwikła JB, et al. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: The CLARINET open-label extension study. Endocr Relat Cancer. 2016;23(3):191–199.
  38. Arnold R, Müller H, Schade-Brittinger C, et al; PROMID Study Group. Placebo-controlled, double-blind, prospective, randomized study of the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: A report from the PROMID study group. J Clin Oncol. 2009; 27(28):4656–4663.
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