title: Molecular alterations in sporadic pancreatic neuroendocrine microadenomas.
abstract: BACKGROUND
  Pancreatic neuroendocrine microadenomas (pNEMAs) are neuroendocrine tumors measuring <5 mm in diameter. They are considered the precursor of pancreatic neuroendocrine tumors (pNETs). The aim of this study was to investigate the immunohistochemical differences between pNEMA, pNET, and hyperplasia of pancreatic islet cells (HPIL) in patients with non-familial syndromes.
  
  
  METHODS
  We evaluated 21 pNEMAs, 19 HPILs, and 21 non-functional pNETs (10 G1 and 11 G2 cases) in patients with non-familial syndromes. Immunohistochemistry for tumor-associated markers death domain-associated protein (DAXX), alpha thalassemia/mental retardation X-linked (ATRX), cytokeratin 19 (CK19), bcl-2, and CD99 was performed.
  
  
  RESULTS
  DAXX was expressed in 95%, 71%, and 71% of HPIL, pNEMA, and pNET samples, respectively; the differences were not significant. ATRX expression in pNEMA and pNET was significantly lower than that in HPIL, whereas there was no significant difference between pNEMA and pNET (HPIL: 95%, pNEMA: 43%, and pNET: 52%). All HPIL and pNEMA cases were negative for bcl-2 and positive for CD99, whereas 29% of pNETs were positive for bcl-2 and 24% were negative for CD99. CK19 expression in HPIL was significantly lower than in pNEMA and pNET, although no significant difference was observed between pNEMA and pNET (HPIL: 5%, pNEMA: 57%, and pNET: 43%). Among G1 and G2 pNETs, CD99 was expressed in 50% of G1 pNETs but not in any G2 pNET cases.
  
  
  CONCLUSIONS
  Non-familial HPIL, pNEMA, and pNET patients exhibit distinct ATRX, CD99, CK19, and bcl-2 molecular profiles.
authors.affiliation: Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hadano
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Japan. Electronic address: kenichi.hirabayashi@tokai.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hirabayashi
authors.affiliation: Department of Surgery, Tokai University School of Medicine, Japan.
authors.forename: Misuzu
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kawanishi
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Takanashi
authors.affiliation: Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Department of Surgery, Tokai University School of Medicine, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakagohri
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: ATRX; DAXX; Microadenoma; Neuroendocrine tumor; Pancreas; Sporadic