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. 2019 May;21(5):612-618.
doi: 10.1016/j.hpb.2018.09.016. Epub 2018 Oct 23.

Limited role of Chromogranin A as clinical biomarker for pancreatic neuroendocrine tumors

Alessandra Pulvirenti  1 , Deepthi Rao  2 , Caitlin A Mcintyre  1 , Mithat Gonen  3 , Laura H Tang  2 , David S Klimstra  2 , Martin Fleisher  4 , Lakshmi V Ramanathan  4 , Diane Reidy-Lagunes  5 , Peter J Allen  6
Affiliations

Limited role of Chromogranin A as clinical biomarker for pancreatic neuroendocrine tumors

Alessandra Pulvirenti et al. HPB (Oxford). 2019 May.

Abstract

Background: Serum Chromogranin A (CgA) is widely used as a biomarker for pancreatic neuroendocrine tumors (PanNETs). The aim of this study was to investigate the value of CgA as a diagnostic and prognostic marker for well-differentiated PanNETs.

Methods: Patients with well-differentiated PanNET and a baseline CgA measurement, between 2011 and 2016 were reviewed. The diagnostic value was determined by comparing CgA values from patients with PanNETs to those with other pancreatic neoplasms and healthy controls. The Kaplan-Meier method was used to investigate the CgA prognostic significance.

Results: Ninety-nine patients met inclusion criteria. As a diagnostic marker, CgA had a sensitivity of 66%, specificity of 95%, and overall accuracy of 71%. The use of PPIs was associated with a higher CgA level (p = 0.015). When excluding patients on PPIs, CgA accuracy in distinguishing PanNETs from other pancreatic neoplasms was 66%, the sensitivity and specificity were 60% and 75% respectively. Elevated CgA (p = 0.004), Ki67% (p < 0.001), tumor grade (p < 0.001) and stage of disease (p = 0.036) were associated with disease-specific survival.

Conclusion: CgA has a limited role as a diagnostic biomarker for well-differentiated PanNETs. An elevated CgA level may have prognostic value but its role should be further investigated with respect to other known pathological factors.

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Figures

Figure 1
Figure 1
Chromogranin A diagnostic value. (A) ROC curve obtained with 99 patients with PanNET and 21 healthy controls. (B) ROC obtained with 65 patients with PanNET not taking PPI and 48 patients with non-neuroendocrine pancreatic neoplasms
Figure 2
Figure 2
Pathological diagnosis ofpatients with non-neuroendocrine pancreatic tumors. *PDAC=pancreatic adenocarcinoma, ACC=acinar cella carcinoma, SPN=solid pseudo-papillary neoplasm, mRCC=metastatic renal clear cell carcinoma, SCA=serous cysticadenoma, PS=pancreatic sarcoma, AC=anaplastic carcinoma
Figure 3
Figure 3
Median with 95% CI CgA serum value in patients with PanNET and with non-PanNET pancreatic tumors (A). Percentage of patients with CgA serum value upper the limit of normal (ULN) according to pathology (B). *Other neoplasm includes: solid pseudo-papillary neoplasm (n=3), metastatic renal clear cell carcinoma (n=2), serous cystadenoma (n=3), pancreatic sarcoma (n=1), anaplastic carcinoma (n=1)
Figure 4
Figure 4
Disease specific survival curve of patients based on CgA levels. Patients with high CgA level (>15 ng/ml) had a significantly poorer survival than patients with low CgA levels (≤15 ng/ml)
See this image and copyright information in PMC

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