title: Clinicopathologic significance of immunostaining of α-thalassemia/mental retardation syndrome X-linked protein and death domain-associated protein in neuroendocrine tumors.
abstract: α-Thalassemia/mental retardation syndrome X-linked protein (ATRX) and death domain-associated protein (DAXX) genes are tumor suppressors whose mutations have been identified in sporadic pancreatic neuroendocrine tumors as well as in patients with MEN1. However, it is unknown whether ATRX and DAXX alterations are specific for pancreatic neuroendocrine tumor. In addition, the association of ATRX/DAXX protein loss with tumor cell proliferation has not been examined. We, therefore, immunostained ATRX and DAXX in 10 gastric, 15 duodenal, 20 rectal, 70 pancreatic, and 22 pulmonary neuroendocrine tumors with 15 nonneoplastic pancreases and 27 pancreatic adenocarcinomas to elucidate the site-specific roles of ATRX/DAXX abnormalities. At least 1 loss of ATRX and DAXX immunoreactivity was detected in all neuroendocrine tumor cases but not in any of nonneoplastic pancreatic tissues or pancreatic adenocarcinomas. The loss of DAXX protein was correlated with the Ki-67 index (ATRX, P = .904; DAXX, P = .044). The status of DAXX immunoreactivity correlated positively with World Health Organization histologic grade (P = .026). These results suggest that the status of ATRX or DAXX protein loss in neuroendocrine tumor differed among the organs in which these tumors arose, and these proteins may play site-specific roles in the development of these tumors.
authors: Department of Pathology, Tohoku University Hospital, Sendai, J980-8574 Japan; Department of Pathology, The Second Hospital of Jilin University, Changchun, 130041 China.
authors: Shi-Fan
authors: SF
authors: Chen
authors: Atsuko
authors: A
authors: Kasajima
authors: Samaneh
authors: S
authors: Yazdani
authors: Monica S M
authors: MS
authors: Chan
authors: Lin
authors: L
authors: Wang
authors: Yang-Yang
authors: YY
authors: He
authors: Hong-Wen
authors: HW
authors: Gao
authors: Hironobu
authors: H
authors: Sasano
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002648:Child; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D038901:X-Linked Intellectual Disability / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000473:pathology*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins; D055815:Young Adult; D017085:alpha-Thalassemia / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; C434957:RYBP protein, human; D012097:Repressor Proteins
keywords: ATRX; DAXX; Neuroendocrine tumors