DAXX, ATRX, and MSI in PanNET and Their Metastases: Correlation with Histopathological Data and Prognosis.

Autor: Gisder DM; Institute of Pathology, Ruhr Universität Bochum, Bochum, Germany., Overheu O; Department of Haematology and Oncology with Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany., Keller J; Institute of Pathology, Ruhr Universität Bochum, Bochum, Germany., Nöpel-Dünnebacke S; Department of Haematology and Oncology with Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany., Uhl W; Katholisches Klinikum Bochum gGmbH, Institute of General and Visceral Surgery, St. Josef-Hospital, Bochum, Germany., Reinacher-Schick A; Department of Haematology and Oncology with Palliative Care, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany., Tannapfel A; Institute of Pathology, Ruhr Universität Bochum, Bochum, Germany., Tischoff I; Institute of Pathology, Ruhr Universität Bochum, Bochum, Germany.
Jazyk: angličtina
Zdroj: Pathobiology : journal of immunopathology, molecular and cellular biology [Pathobiology] 2023; Vol. 90 (2), pp. 71-80. Date of Electronic Publication: 2022 Jun 10.
DOI: 10.1159/000524920
Abstrakt: Introduction: Studies on pancreatic neuroendocrine tumors (PanNETs) regarding loss of ATRX, DAXX, or frequency of microsatellite instability (MSI) show inconclusive results. So far, data on corresponding metastaseshave not been published.
Methods: We performed immunohistochemistry (IHC) of ATRX, DAXX, MSH2, MSH6, MLH1, and PMS2 on 74 PanNETs and 19 metastases. ATRX- and DAXX-negative PanNETs were further sequenced for mutations. We used polymerase chain reaction for MSI on cases with IHC loss of MSH2, MSH6, MLH1, and PMS2.
Results: Immunohistochemical loss of DAXX and ATRX was observed in 8/74 (11%) and 6/74 (8%) PanNETs. Loss of DAXX immunoreactivity was statistically associated with higher tumor grade and showed a tendency toward a decreased overall survival. Sequencing of DAXX- (7/11 [64%]) and ATRX-negative (5/11 [45%]) PanNETs revealed a mutation in 6/7 (86%) and 2/5 (40%). The specificity of immunohistochemical loss of DAXX and ATRX for mutation was 80% and 67%, respectively. The expression status of DAXX compared to primary tumor differs in 2/12 (17%) lymph node metastases. We further identified 3/74 (4%) tumors as MSI, associated with a poor prognosis.
Discussion/conclusion: Our study supports the hypothesis that a loss of DAXX immunoreactivity can identify a more aggressive subtype of PanNET with high confidence, while ATRX loss is a weaker indicator. Our results also strengthen the role of DAXX immunolabeling as a prognostic marker. We could show that ATRX might be less suitable as a surrogate for sequencing. Our results indicate that IHC of DAXX and ATRX may identify PanNET subtypes as targets for more aggressive therapy.
(© 2022 S. Karger AG, Basel.)
Databáze: MEDLINE
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