Study of clinicopathological features, hormone immunoexpression, and loss of ATRX and DAXX expression in pancreatic neuroendocrine tumors

Abstract

ABSTRACTObjectives: 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%). Conclusion: 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.