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. 2025 Sep;89(3):910-920.
doi: 10.1007/s12020-025-04291-y. Epub 2025 Jun 2.

Chromogranin a and pancreatic polypeptide are not suitable for the screening of pancreatic neuroendocrine tumors in MEN1 - a long-term follow-up study

Iiro Kostiainen  1 , Susanna Majala  2   3 , Jukka Schildt  4 , Helka Parviainen  5   6 , Saila Kauhanen  2   3 , Niina Matikainen  7 , Eeva M Ryhänen  7 , Camilla Schalin-Jäntti  7
Affiliations

Chromogranin a and pancreatic polypeptide are not suitable for the screening of pancreatic neuroendocrine tumors in MEN1 - a long-term follow-up study

Iiro Kostiainen et al. Endocrine. 2025 Sep.

Abstract

Purpose: In patients with multiple endocrine neoplasia type 1 (MEN1) followed up at ENETS centers of Excellence, chromogranin A (CgA) and pancreatic polypeptide (PP) are widely used screening tools for pancreatic neuroendocrine tumors (panNETs). Previous studies have demonstrated conflicting results regarding their performance in MEN1. This retrospective study aims to bring clarity to the question by investigating a well-characterized MEN1 cohort. We studied the impact of long-term biomarker follow-up on the clinical management of panNETs in MEN1.

Methods: We calculated the sensitivity and specificity and performed ROC analysis of CgA and PP for diagnosing any panNET, ≥20 mm panNET, and metastatic panNET in comparison to imaging reference standard in 58 MEN1 patients. All patients had undergone somatostatin receptor PET/CT and conventional imaging. Longitudinal impact of 10-year annual biomarker measurements on real-life clinical management was analyzed from patient records.

Results: Sensitivity of CgA (n = 48) and PP (n = 47) for diagnosing any panNET, ≥20 mm panNET, and metastatic panNET was 35%, 30%, and 60 and 23%, 33%, and 0%, respectively. For CgA, the AUC for diagnosing any panNET, ≥20 mm panNET, and metastatic panNET was 0.30 (95% CI 0.09-0.51), 0.49 (95% CI 0.29-0.68), and 0.69 (95% CI 0.42-0.95), respectively. For PP, the AUC for detection of metastatic panNET was 0.28 (95% CI 0.11-0.46). The annual biomarker measurements during 514 patient-years of follow-up did not affect the clinical management of panNETs.

Conclusion: CgA and PP are not helpful in diagnosing panNETs in MEN1. It is time to revise the surveillance protocols in practice.

Keywords: Chromogranin A; MEN1; Pancreatic neuroendocrine tumor; Pancreatic polypeptide; Somatostatin receptor PET/CT.

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Conflict of interest statement

Compliance with ethical standards. Conflict of interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of patients included in the analyses comparing biomarker performance to the reference standard. *Lung neuroendocrine tumor (n = 5), duodenal neuroendocrine tumor (n = 2), mediastinal neuroendocrine carcinoma (n = 1), diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (n = 1)
Fig. 2
Fig. 2
Scatter plots comparing biomarkers with the number of pancreatic neuroendocrine tumors (panNET) detected in somatostatin receptor positron emission tomography/computed tomography (SSTR PET/CT), size of the largest panNET and glomerular filtration rate (GFR). Horizontal dotted Line denotes the upper limit of normal (ULN) for biomarker concentration
Fig. 3
Fig. 3
Dot plots comparing levels of biomarkers with panNET stage. Horizontal dotted line denotes upper limit of normal (ULN) for biomarker concentration
Fig. 4
Fig. 4
Receiver operator characteristics (ROC) analysis of biomarker performance for clinically relevant endpoints. 95% CI of the area under the curve (AUC) in parentheses
See this image and copyright information in PMC

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