Loss of Expression of DAXX and ATRX in Low-Grade Neuroendocrine Tumors (Carcinoid Tumors)
Qing Zhao, Shaofan Weng, Wai Chin Foo, Jeannelyn S Estrella, James C Yao, Hua Wang, Huamin Wang, Asif Rashid. The University of Texas MD Anderson Cancer Center, Houston, TX
Background: DAXX, a protein associated with FAS-mediated apoptosis, and ATRX, SWI/SNF-2 family chromatin remodeler, form a complex that has been associated with deposition of histone H3.3 at heterochromatin region of the genome. Recently, DAXX and ATRX genes were found to be frequently altered in pancreatic endocrine tumors. Tumors with these mutations were associated with a better overall survival. Loss of immunolabeling for DAXX and ATRX correlate with mutation of the respective genes. It is largely unknown whether the altered expression of DAXX and/or ATRX protein are present in neuroendocrine tumors other than pancreatic origin.
Design: Tissue microarrays consisting of 73 patients with pancreatic endocrine tumors; 53 patients with small bowel, stomach or colorectal neuroendocrine tumors; and 16 patients with pulmonary neuroendocrine tumors. These were low to intermediate-grade neuroendocrine tumors. Immunohistochemical studies were performed on paraffin-fixed tissue microarray sections. Nuclear staining was scored as negative (lack of staining) or positive. These staining results were correlated with clinicopathological data, including patients overall survival, by Chi-square and Kaplan-Meier analyses.
Results: Loss of expression of DAXX was present in 33/61 (54%) pancreatic endocrine tumors, 8/42 (19%) gastrointestinal neuroendocrine tumors, and 8/15 (53%) pulmonary neuroendocrine tumors. There was significant difference in loss of DAXX staining result among pancreatic neuroendocrine tumors and neuroendocrine tumor of other sites (p=0.001). In contrast, loss of expression of ATRX was found in 17/63 (27%) pancreatic endocrine tumors, 12/42 (27%) gastrointestinal neuroendocrine tumors, and 5/16 (31%) pulmonary neuroendocrine tumors. There was no significant difference in loss of ATRX staining results among pancreatic neuroendocrine tumors and neuroendocrine tumor from any other sites. Loss of either protein was not associated with patients overall survival, including each subsite.
Conclusions: Loss of nuclear expression DAXX and ATRX was frequent observed in pancreatic neuroendocrine tumor and neuroendocrine tumors from other sites. However, loss of either protein was not associated with patients overall survival.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 71, Wednesday Morning