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Updated: Apr 7, 2026
Simulating Pancreatic Neuroplasticity: In Vitro Dual-neuron Plasticity Assay
Published on: April 14, 2014
Serotonin Expression and β-Cell Phenotype Are Associated With Indolent Behavior in Pancreatic Neuroendocrine Tumors
Annika L Windon1, Frank Revetta1, Wei Chen2
1Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Background And Objectives:
ARX and PDX1 transcription factors have been considered indicators of the cell of origin for pancreatic neuroendocrine tumors (PanNETs). Some PanNETs show dense fibrosis (sclerosing morphology) and an association with serotonin expression. This study aimed to explore ARX and PDX1 expression in these tumors.
Methods:
Pathology archives were searched from 2005 to 2019 for PanNETs with dense stromal fibrosis. Immunohistochemical stains for ARX, PDX1, and serotonin were performed and reviewed with pertinent clinical findings.
Results:
Fifty-one PanNETs were evaluated. Serotonin expression was identified in 19 (37%) tumors. The mean tumor size was smaller in the serotonin-expressing group compared to the non-expressing group (1.7 ± 1.1 vs. 2.5 ± 1.2 cm, p = 0.03). Serotonin-expressing tumors demonstrated a β-cell phenotype with absence of ARX expression in the majority of tumors (n = 16; 84.2%), while the non-expressing tumors demonstrated an α-cell phenotype with ARX expression (n = 24, 75%, p < 0.01). Synchronous/metachronous liver metastasis was more frequent in the serotonin non-expressing tumors (p = 0.020). Serotonin expression was associated with a better disease-free survival.
Conclusions:
Serotonin-expressing PanNETs more commonly showed a β-cell phenotype, while non-expressing tumors favored an α-cell phenotype with more frequent liver metastasis. The expression of serotonin suggests more indolent behavior in this variant of PanNETs.
