Utility of chromogranin A, pancreatic polypeptide, glucagon and gastrin in the diagnosis and follow‐up of pancreatic neuroendocrine tumours in multiple endocrine neoplasia type 1 patients

Abstract

Objective Pancreatic neuroendocrine tumors (PNETs) are the major source of disease-specific mortality in multiple endocrine neoplasia type 1 (MEN1) patients. Chromogranin A (CgA), pancreatic polypeptide (PP), glucagon, and gastrin have some diagnostic value in sporadic PNETs, but there is very little evidence for their efficacy in diagnosing PNETs in MEN1 patients. Design We performed a retrospective chart review of the existing MEN1 database in our institution. Patients One hundred thirteen patients were eligible for diagnostic value analysis of tumor markers. Patients were excluded if measurement of tumor markers was missing, either 3 months prior to PNETs diagnosis (PNETs patients) or prior to abdominal imaging (non-PNETs patients). Measurements Clinicopathologic characteristics and of tumor marker measurements were analyzed. Results Of 293 confirmed MEN1 cases, 55 PNETs and 58 non-PNETs met inclusion criteria. The area under the curve (AUC) for CgA, PP, glucagon, and gastrin in MEN1 cases was 59.5%, 64.1%, 77.0%, and 75.9%, respectively. The AUC for the combination of CgA, PP, and gastrin was 59.6%. PP, but not CgA, glucagon or gastrin was significantly associated with both age and PNETs functional status (P=0.0485 and 0.0188, respectively). No markers were significantly associated with sex, PNETs tumor size, tumor number, tumor location, AJCC (American Joint Committee on Cancer) stage, presence of lymph node metastasis, lymphovascular invasion, or overall survival. CgA values were not significantly lower following PNETs resection than pre-operatively (P=0.554). Conclusions The value of blood markers for diagnosing PNETs in MEN1 patients is relatively low, even when used in combination.

Diagnosing Nonfunctional Pancreatic NETs in MEN1: The Evidence Base

“…Two studies had maximum applicability for this review [11, 12]. de Laat et al [12] had the lowest overall risk of bias and estimated the accuracy of CgA in 81 consecutive Dutch MEN1 patients.…”

Is estrogen exposure a protective factor for pancreatic neuroendocrine tumours in female patients with multiple endocrine neoplasia syndrome type 1?

“…As PNETs are the most common cause of death in patients with MEN1, it is important to identify them as early as possible. We and other researchers have shown that existing circulating PNET tumour markers do not have sufficient diagnostic value in patients with MEN1 . Therefore, it is essential to identify alternative and additional risk factors for PNETs to improve early detection and potentially the prognosis of these patients.…”

“…We and other researchers have shown that existing circulating PNET tumour markers do not have sufficient diagnostic value in patients with MEN1. 25,26 Therefore, it is essential to identify alternative and additional risk factors for PNETs to improve early detection and potentially the prognosis of these patients. In this study, we could not confirm that estrogen exposure had a protective effect against PNET risk; this was consistent with what was found in one study of pancreatic cancer, 25 although another study found the opposite result.…”

“…25,26 Therefore, it is essential to identify alternative and additional risk factors for PNETs to improve early detection and potentially the prognosis of these patients. In this study, we could not confirm that estrogen exposure had a protective effect against PNET risk; this was consistent with what was found in one study of pancreatic cancer, 25 although another study found the opposite result. 27 Our study identified a significant correlation of CEET with PNET size (P = 0Á043), with longer estrogen exposure in the ≤1Á55 cm group and shorter exposure in the >1Á55 cm group, suggesting that estrogen might have a protective effect against PNET growth.…”

Neuroendokrine Tumoren in der täglichen gastroenterologischen und endoskopischen Praxis – ein klinisch orientierter Leitfaden

“…Bei MEN-1-Patienten fand sich jüngst in einer großangelegten Untersuchung ein geringer Wert von CgA, PP, Glukagon und Gastrin hinsichtlich der Diagnose, Tumorgröße, Stadium, Metastasen oder Prognose eines Pankreas-NET [77].…”