title: Study of clinicopathological features, hormone immunoexpression, and loss of ATRX and DAXX expression in pancreatic neuroendocrine tumors.
abstract: OBJECTIVE
  Neuroendocrine tumors of the pancreas (PanNETs) are rare neoplasms, and not much is known about their pathogenesis. We aimed to evaluate ATRX/DAXX immunoexpression in PanNETs a cohort of well-characterized PanNETs.
  
  
  METHODS
  PanNETs diagnosed over a 10-year period were retrieved and clinicopathogical features reviewed. Immuohistochemistry for pancreatic hormones, and for ATRX and DAXX was performed.
  
  
  RESULTS
  Sixty-eight PanNETs were included (30 males and 38 females) with median age of 39 years. Histologically, there were 37 Grade 1 (54.4%), 27 Grade 2 (39.7%), and 4 Grade 3 (5.9%) cases. On immunostaining for hormones, insulin expression was most frequent (22 cases; 38.6%), followed by gastrin (7 cases; 12.3%); 25 cases (43.9%) were negative for all hormones. Loss of ATRX/DAXX immunoexpression was noted in 18 cases (39.1%), and was significantly more frequent in tumors larger than 5 cm. Lymphovascular invasion, infiltrative borders, and infiltration of adjacent organs were also more frequent in tumors with loss of ATRX/DAXX immunoreactivity. A little over half the tumors with ATRX/DAXX loss showed negative immunostaining for all hormones (55.6%).
  
  
  CONCLUSIONS
  Loss of ATRX/DAXX expression is frequent in PanNETs, indicating a role in their pathogenesis. As ATRX/DAXX loss is more frequent in larger tumors, and in those with lymphovascular invasion, adjacent organ infiltration and infiltrative borders, this suggests that loss of ATRX/DAXX expression is a late event in pathogenesis and is associated with an aggressive phenotype. Immunohistochemical detection of ATRX/DAXX loss is a simple method for ATRX/DAXX evaluation and can easily be incorporated into routine pathological evaluation of PanNETs.
authors.affiliation: a Departments of Pathology and Medical Oncology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Rajni
authors.initials: R
authors.lastname: Yadav
authors.affiliation: a Departments of Pathology and Medical Oncology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Aanchal
authors.initials: A
authors.lastname: Kakkar
authors.affiliation: a Departments of Pathology and Medical Oncology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Atul
authors.initials: A
authors.lastname: Sharma
authors.affiliation: a Departments of Pathology and Medical Oncology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Prabhat Singh
authors.initials: PS
authors.lastname: Malik
authors.affiliation: a Departments of Pathology and Medical Oncology , All India Institute of Medical Sciences , New Delhi , India.
authors.forename: Mehar Chand
authors.initials: MC
authors.lastname: Sharma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis* / Q000276:immunology; D000328:Adult; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000032:analysis* / Q000276:immunology; D005260:Female; D005755:Gastrins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis; D008297:Male; D018832:Molecular Chaperones; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis* / Q000276:immunology; D010187:Pancreatic Hormones; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D000075924:X-linked Nuclear Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D005755:Gastrins; D007328:Insulin; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D010187:Pancreatic Hormones; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: ATRX; DAXX; immunohistochemistry; neuroendocrine tumor; pancreas