Low accuracy of chromogranin A for diagnosing early‑stage pancreatic neuroendocrine tumors

Tseng,Chao‑Ming; Cheng,Tsu‑Yao; Chen,Tai‑Been; Tien,Yu‑Wen; Chen,Chien‑Chuan; Lin,Jaw‑Town; Wang,Hsiu‑Po

doi:10.3892/ol.2018.8472

Low accuracy of chromogranin A for diagnosing early‑stage pancreatic neuroendocrine tumors

Authors:
- Chao‑Ming Tseng
- Tsu‑Yao Cheng
- Tai‑Been Chen
- Yu‑Wen Tien
- Chien‑Chuan Chen
- Jaw‑Town Lin
- Hsiu‑Po Wang
View Affiliations

Affiliations: Department of Internal Medicine, E‑Da Cancer Hospital/I‑Shou University, Kaohsiung 824, Taiwan, R.O.C., Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan, R.O.C., Department of Medical Imaging and Radiological Sciences, I‑Shou University, Kaohsiung 824, Taiwan, R.O.C., Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan, R.O.C., Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan, R.O.C., School of Medicine, Fu Jen Catholic University, New Taipei City 10002, Taiwan, R.O.C.
Published online on: April 12, 2018 https://doi.org/10.3892/ol.2018.8472
Pages: 8951-8958
Copyright: © Tseng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to evaluate the clinical utility of plasma chromogranin A (CgA) in patients diagnosed with early‑stage pancreatic neuroendocrine tumors (PNETs) in terms of diagnostic value and treatment response. A total of 35 patients with PNETs were prospectively enrolled from August 2010 to April 2014. Demographic and clinicopathological data were collected, and serial plasma CgA levels were measured. Tumor responses were defined by the Response Evaluation Criteria In Solid Tumors criteria. Pearson's χ2 test was used for the analysis of the association between the plasma CgA level and various factors. Plasma CgA level was significantly associated with the size (P=0.03), metastasis (P=0.02) and tumor stage (P=0.03) of the PNETs. Using 126 U/l as the optimal cutoff value, the sensitivity and specificity were 87.5 and 81.5%, respectively. For localized tumors, the sensitivity of CgA for diagnosing PNETs was relatively low, even following a lowering of the cutoff values (29.6‑51.9%). Plasma CgA level was correlated with therapeutic response in those patients with high baseline CgA levels (P=0.025), but not in the patients with low baseline CgA levels (P=0.587). In conclusion, plasma CgA level was associated with tumor size, metastasis and tumor stage in patients with PNET. For early‑stage PNETs, CgA exhibited a limited role in diagnosis and treatment response evaluation in the population of the present study.

View Figures

View References

1	Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, Shih T and Yao JC: Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 3:1335–1342. 2017. View Article : Google Scholar : PubMed/NCBI
2	Yao JC, Pavel M, Phan AT, Kulke MH, Hoosen S, St Peter J, Cherfi A and Öberg KE: Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. J Clin Endocrinol Metab. 96:3741–3749. 2011. View Article : Google Scholar : PubMed/NCBI
3	Milan SA and Yeo CJ: Neuroendocrine tumors of the pancreas. Curr Opin Oncol. 24:46–55. 2012. View Article : Google Scholar : PubMed/NCBI
4	Tsai HJ, Wu CC, Tsai CR, Lin SF, Chen LT and Chang JS: The epidemiology of neuroendocrine tumors in taiwan: A nation-wide cancer registry-based study. PLoS One. 8:e624872013. View Article : Google Scholar : PubMed/NCBI
5	Burns WR and Edil BH: Neuroendocrine pancreatic tumors: Guidelines for management and update. Curr Treat Options Oncol. 13:24–34. 2012. View Article : Google Scholar : PubMed/NCBI
6	Modlin IM, Gustafsson BI, Moss SF, Pavel M, Tsolakis AV and Kidd M: Chromogranin A-biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol. 17:2427–2443. 2010. View Article : Google Scholar : PubMed/NCBI
7	Lawrence B, Gustafsson BI, Kidd M, Pavel M, Svejda B and Modlin IM: The clinical relevance of chromogranin A as a biomarker for gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 40(111–134): viii2011.
8	Vinik AI, Woltering EA, Warner RR, Caplin M, O'Dorisio TM, Wiseman GA, Coppola D and Go VL: North American Neuroendocrine Tumor Society (NANETS): NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 39:713–734. 2010. View Article : Google Scholar : PubMed/NCBI
9	Jilesen AP, Busch OR, van Gulik TM, Gouma DJ and van Dijkum Nieveen EJ: Standard pre- and postoperative determination of chromogranin a in resectable non-functioning pancreatic neuroendocrine tumors-diagnostic accuracy: NF-pNET and low tumor burden. Dig Surg. 31:407–414. 2014. View Article : Google Scholar : PubMed/NCBI
10	Shanahan MA, Salem A, Fisher A, Cho CS, Leverson G, Winslow ER and Weber SM: Chromogranin A predicts survival for resected pancreatic neuroendocrine tumors. J Surg Res. 201:38–43. 2016. View Article : Google Scholar : PubMed/NCBI
11	Chou WC, Hung YS, Hsu JT, Chen JS, Lu CH, Hwang TL, Rau KM, Yeh KY, Chen TC and Sun CF: Chromogranin A is a reliable biomarker for gastroenteropancreatic neuroendocrine tumors in an Asian population of patients. Neuroendocrinology. 95:344–350. 2012. View Article : Google Scholar : PubMed/NCBI
12	Han X, Zhang C, Tang M, Xu X, Liu L, Ji Y, Pan B and Lou W: The value of serum chromogranin A as a predictor of tumor burden, therapeutic response, and nomogram-based survival in well-moderate nonfunctional pancreatic neuroendocrine tumors with liver metastases. Eur J Gastroenterol Hepatol. 27:527–535. 2015. View Article : Google Scholar : PubMed/NCBI
13	Hijioka M, Ito T, Igarashi H, Fujimori N, Lee L, Nakamura T, Jensen RT and Takayanagi R: Serum chromogranin A is a useful marker for Japanese patients with pancreatic neuroendocrine tumors. Cancer Sci. 105:1464–1471. 2014. View Article : Google Scholar : PubMed/NCBI
14	Qiao XW, Qiu L, Chen YJ, Meng CT, Sun Z, Bai CM, Zhao DC, Zhang TP, Zhao YP, Song YL, et al: Chromogranin A is a reliable serum diagnostic biomarker for pancreatic neuroendocrine tumors but not for insulinomas. BMC Endocr Disord. 14:642014. View Article : Google Scholar : PubMed/NCBI
15	Yung RC, Otell S, Illei P, Clark DP, Feller-Kopman D, Yarmus L, Askin F, Gabrielson E and Li QK: Improvement of cellularity on cell block preparations using the so-called tissue coagulum clot method during endobronchial ultrasound-guided transbronchial fine-needle aspiration. Cancer Cytopathol. 120:185–195. 2012. View Article : Google Scholar : PubMed/NCBI
16	Chatzipantelis P, Salla C, Konstantinou P, Karoumpalis I, Sakellariou S and Doumani I: Endoscopic ultrasound-guided fine-needle aspiration cytology of pancreatic neuroendocrine tumors: A study of 48 cases. Cancer. 114:255–262. 2008. View Article : Google Scholar : PubMed/NCBI
17	Bosman FT, Carneiro F, Hruban RH and Theise ND: WHO classification of tumours of the digestive system: World Health Organization. 2010.
18	Edge SB, Byrd DR, Compton CC, Fritz AG, Greene F and Trotti A: AJCC Cancer Staging Manual. New York, NY: Springer; 2010
19	Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI
20	Vinik AI, Silva MP, Woltering EA, Go VL, Warner R and Caplin M: Biochemical testing for neuroendocrine tumors. Pancreas. 38:876–889. 2009. View Article : Google Scholar : PubMed/NCBI
21	Nölting S, Kuttner A, Lauseker M, Vogeser M, Haug A, Herrmann KA, Hoffmann JN, Spitzweg C, Göke B and Auernhammer CJ: Chromogranin a as serum marker for gastroenteropancreatic neuroendocrine tumors: A single center experience and literature review. Cancers (Basel). 4:141–155. 2012. View Article : Google Scholar : PubMed/NCBI
22	Campana D, Nori F, Piscitelli L, Morselli-Labate AM, Pezzilli R, Corinaldesi R and Tomassetti P: Chromogranin A: Is it a useful marker of neuroendocrine tumors? J Clin Oncol. 25:1967–1973. 2007. View Article : Google Scholar : PubMed/NCBI
23	Walter T, Chardon L, Chopin-laly X, Raverot V, Caffin AG, Chayvialle JA, Scoazec JY and Lombard-Bohas C: Is the combination of chromogranin A and pancreatic polypeptide serum determinations of interest in the diagnosis and follow-up of gastro-entero-pancreatic neuroendocrine tumours? Eur J Cancer. 48:1766–1773. 2012. View Article : Google Scholar : PubMed/NCBI
24	Cherenfant J, Stocker SJ, Gage MK, Du H, Thurow TA, Odeleye M, Schimpke SW, Kaul KL, Hall CR, Lamzabi I, et al: Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors. Surgery. 154:785–793. 2013. View Article : Google Scholar : PubMed/NCBI
25	Metz DC and Jensen RT: Gastrointestinal neuroendocrine tumors: Pancreatic endocrine tumors. Gastroenterology. 135:1469–1492. 2008. View Article : Google Scholar : PubMed/NCBI
26	Kishi Y, Shimada K, Nara S, Esaki M, Hiraoka N and Kosuge T: Basing treatment strategy for non-functional pancreatic neuroendocrine tumors on tumor size. Ann Surg Oncol. 21:2882–2888. 2014. View Article : Google Scholar : PubMed/NCBI
27	Paik WH, Ryu JK, Song BJ, Kim J, Park JK, Kim YT and Yoon YB: Clinical usefulness of plasma chromogranin a in pancreatic neuroendocrine neoplasm. J Korean Med Sci. 28:750–754. 2013. View Article : Google Scholar : PubMed/NCBI
28	Korse CM, Taal BG, Vincent A, van Velthuysen ML, Baas P, Buning-Kager JC, Linders TC and Bonfrer JM: Choice of tumour markers in patients with neuroendocrine tumours is dependent on the histological grade. A marker study of Chromogranin A, Neuron specific enolase, Progastrin-releasing peptide and cytokeratin fragments. Eur J Cancer. 48:662–671. 2012. View Article : Google Scholar : PubMed/NCBI
29	Jensen EH, Kvols L, McLoughlin JM, Lewis JM, Alvarado MD, Yeatman T, Malafa M and Shibata D: Biomarkers predict outcomes following cytoreductive surgery for hepatic metastases from functional carcinoid tumors. Ann Surg Oncol. 14:780–785. 2007. View Article : Google Scholar : PubMed/NCBI
30	de Laat JM, Pieterman CR, Weijmans M, Hermus AR, Dekkers OM, de Herder WW, van der Horst-Schrivers AN, Drent ML, Bisschop PH, Havekes B, et al: Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients. J Clin Endocrinol Metab. 98:4143–4151. 2013. View Article : Google Scholar : PubMed/NCBI
31	Granberg D, Stridsberg M, Seensalu R, Eriksson B, Lundqvist G, Oberg K and Skogseid B: Plasma chromogranin A in patients with multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 84:2712–2717. 1999. View Article : Google Scholar : PubMed/NCBI
32	Giusti M, Sidoti M, Augeri C, Rabitti C and Minuto F: Effect of short-term treatment with low dosages of the proton-pump inhibitor omeprazole on serum chromogranin A levels in man. Eur J Endocrinol. 150:299–303. 2004. View Article : Google Scholar : PubMed/NCBI