Association Between Endoscopic Ultrasound Based Preoperative ATRX/DAXX Immunohistochemistry Expression and Prognosis of Sporadic, Non-FunctiOnal pancREatic Neuroendocrine tumorS: a prospEctivE Cohort Study
| Registry | NCT06406387, acronym FORESEE |
|---|---|
| Status | Active not recruiting |
| Study type | Observational |
| Enrollment | 100 (Actual) |
| Sponsor | Azienda Ospedaliera Universitaria Integrata Verona (Other) |
| Conditions | Pancreatic Neuroendocrine Tumor |
| Interventions | ATRX/DAXX immunohistochemistry (Diagnostic test) |
| Dates | start 2024-06-01, primary completion 2025-03-30, completion 2029-11-30 (estimated), first posted 2024-05-09, last updated 2026-01-13 |
| Locations | 1 site in Italy |
Related Papers Related Patents Related Grants Related Experts
All trials for Pancreatic Neuroendocrine Tumor All trials of ATRX/DAXX immunohistochemistry
P-NENs are classified as functional (F-) or non-functional (NF-) depending on the presence or absence of a clinical hormonal hypersecretion syndrome. Moreover, the WHO 2017 classification of pNENs distinguishes between well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs). pNETs are then divided according to a grading scheme based on Ki67 index in pNETs-G1 (Ki67 index ≤3%) and pNETs-G2 (Ki67 index between 4% and 20%). pNECs are all G3, with a Ki67 index >20%. Endoscopic ultrasound with fine-needle biopsy (EUS-FNB) demonstrated safe and effective preoperative grading based on the Ki-67 proliferative index. However, downstaging rate is not neglectable, reaching 15% in a recent metanalysis. Moreover, recent whole-exome and whole genome sequencing studies revealed that the mutually exclusive inactivating mutations in death domain-associated protein (DAXX) and/or in α-thalassemia/mental retardation X-linked (ATRX) chromatin remodeling genes are associated with more aggressive disease. In a retrospective study, the investigators recently evaluated the correspondence of DAXX/ATRX expression on 41 EUS-FNB samples with corresponding surgical specimens demonstrating a 95.1% (almost perfect agreement, κ = 0.828; p < 0.001) and 92.7% (substantial agreement, κ = 0.626; p < 0.001) concordance for DAXX and ATRX expression, respectively. This study aims to evaluate the potential clinical/prognostic role of DAXX/ATRX expression as implementation of the currently used Ki67-based grading, evaluated on EUS-FNB samples in a prospective cohort of patients with NF-pNETs
| Arm | Type | Interventions | Description |
|---|---|---|---|
| ATRX/DAXX loss | Diagnostic Test: ATRX/DAXX immunohistochemistry | The "positive" group including patients with loss of DAXX or ATRX expression evaluated on immunohistochemistry on endoscopic ultrasound biopsy specimens | |
| ATRX/DAXX preserved | Diagnostic Test: ATRX/DAXX immunohistochemistry | The "negative" group including those with preserved DAXX and ATRX expression evaluated on immunohistochemistry on endoscopic ultrasound biopsy specimens |
Sex: All, ages: 18 Years to any
Inclusion Criteria: * Age ≥18 years * Cyto/histologic diagnosis of pNETs * Signed informed consent Exclusion Criteria: * Functional pNETs * Multiple pancreatic nodules * Diagnosis of MEN-1 or Von-Hippel Lindau * Mixed types (e.g., mixed neuroendocrine-acinar/adenocarcinoma) or neuroendocrine carcinomas * Predominantly cystic lesions (more than 50% of the volume). * Metastatic tumors at the time of diagnosis * Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma * Use of anticoagulants that cannot be discontinued * INR >1.5 or platelet count <50.000 * Pregnancy or breastfeeding * Failure to sign the patient's or closest relative's informed consent
| Facility | City | Country | Status |
|---|---|---|---|
| University Hospital of Verona | Verona | Italy |