Subtyping of pancreatic neuroendocrine tumors by transcription factors, hormones, histology, and patient outcome
- 08.10.2024
- Referate: Preisträgerinnen und Preisträger – Promotionspreis
Erschienen in:
- Verfasst von
- Elisa Moser
- Ayako Ura
- Günter Klöppel
- Atsuko Kasajima
- Erschienen in
- Die Pathologie | Sonderheft 1/2024
Abstract
Background
Pancreatic neuroendocrine tumors (PanNETs) show pronounced heterogeneity in terms of hormone and transcription factor (TF) expression. TFs such as ARX and PDX1 are related to alpha- and beta-cell-type features, respectively, and partly associate with patient outcome. However, detailed studies correlating hormone expression, histology, and clinical data are lacking.
Objective
The aim of this study was to identify subtypes of PanNETs that associate with histological, hormonal, and prognostic findings.
Methods
A total of 185 resected PanNETs were divided into five subtypes (types A1, A2, B, C, and D) by cluster analysis based on expression of four TFs (ARX, PDX1, ISL1, and CDX2) and correlated to the expression of hormones and DAXX/ATRX as well as ALT activation status, histology, and progression-free survival.
Results
Subgroup A1 (ISL1+/ARX+/PDX−/CDX2−) was most frequent (46%), followed by type B (18%; ISL1+/ARX−/PDX+/CDX2−), A2 (15%; ISL1+/ARX+/PDX+/CDX2−), C (15%; ISL1−/ARX−/PDX−/CDX2−), and D (5%; ISL1−/ARX−/PDX+/CDX2+). Subgroups A1 and A2 showed a strong association with a trabecular growth pattern and glucagon and pancreatic polypeptide (PP) expression (p < 0.001), while A2 was in addition associated with gastrin expression. Subgroup B was associated with insulin production (p < 0.001) and included all 17 insulinomas. Subgroup C was associated with solid morphology and expression of serotonin, calcitonin, and adrenocorticotropic hormone (ACTH). Subgroup D showed solid morphology, expression of ACTH, somatostatin, or serotonin and had the shortest disease-free survival (p < 0.01). ALT positivity was associated with poorer outcome in types A1 and A2 but not in other types.
Conclusion
PanNETs can be categorized into five subgroups based on different TF signatures, which associate strongly with histology, hormone production, functionality, and patient outcome.
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- Titel
- Subtyping of pancreatic neuroendocrine tumors by transcription factors, hormones, histology, and patient outcome
- Verfasst von
-
Elisa Moser
Ayako Ura
Günter Klöppel
Atsuko Kasajima
- Publikationsdatum
- 08.10.2024
- Verlag
- Springer Medizin
- Erschienen in
-
Die Pathologie / Ausgabe Sonderheft 1/2024
Print ISSN: 2731-7188
Elektronische ISSN: 2731-7196 - DOI
- https://doi.org/10.1007/s00292-024-01367-w
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