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Clinical implications of cell-of-origin epigenetic characteristics in non-functional pancreatic neuroendocrine tumors.
Dreijerink, Koen Ma; Hackeng, Wenzel M; Singhi, Aatur D; Heaphy, Christopher M; Brosens, Lodewijk Aa.
Afiliação
  • Dreijerink KM; Amsterdam Center for Endocrine and Neuroendocrine Tumors, Department of Endocrinology, Amsterdam University Medical Centers, VU University Medical Center, Amsterdam, The Netherlands.
  • Hackeng WM; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Singhi AD; Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Heaphy CM; Departments of Medicine and Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Brosens LA; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
J Pathol ; 256(2): 143-148, 2022 02.
Article em En | MEDLINE | ID: mdl-34750813
ABSTRACT
Primary non-functional pancreatic neuroendocrine tumors (NF-PanNETs) are a heterogeneous group of neuroendocrine neoplasms that display highly variable clinical behavior. Therefore, NF-PanNETs often present clinical teams with a dilemma the uncertain metastatic potential of the tumor has to be weighed against the morbidity associated with surgical resection. Thus, rather than utilizing current radiologic thresholds, there is an urgent need for improved prognostic biomarkers. Recent studies aimed at understanding the epigenetic underpinnings of NF-PanNETs have led to the identification of tumor subgroups based on histone modification and DNA methylation patterns. These molecular profiles tend to resemble the cellular origins of PanNETs. Subsequent retrospective analyses have demonstrated that these molecular signatures are of prognostic value and, importantly, may be useful in the preoperative setting. These studies have highlighted that sporadic NF-PanNETs displaying biomarkers associated with disease progression and poor prognosis, such as alternative lengthening of telomeres, inactivating alpha thalassemia/mental retardation X-linked (ATRX) or death domain-associated protein (DAXX) gene mutations, or copy number variations, more often display alpha cell characteristics. Conversely, NF-PanNETs with beta cell characteristics often lack these unfavorable biomarkers. Alternative lengthening of telomeres, transcription factor protein expression, and possibly DNA methylation can be assessed in endoscopic ultrasound-guided tumor biopsies. Prospective studies focusing on cell-of-origin and epigenetic profile-driven decision making prior to surgery are likely to be routinely implemented into clinical practice in the near future. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Biomarcadores Tumorais / Carcinoma Neuroendócrino / Linhagem da Célula / Epigênese Genética Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Biomarcadores Tumorais / Carcinoma Neuroendócrino / Linhagem da Célula / Epigênese Genética Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article