title: Aberrant expression of human achaete-scute homologue gene 1 in the gastrointestinal neuroendocrine carcinomas.
abstract: OBJECTIVE
  Gastrointestinal neuroendocrine carcinoma (NEC) is extremely aggressive, but its pathophysiologic features remain poorly understood. There have been no biologically specific markers for this disease. In this study, distinctive up-regulation of human achaete-scute homologue 1 (hASH1) in gastrointestinal NECs was clarified.
  
  
  METHODS
  Expression of hASH1 in NECs (n=10), carcinoid tumors (n = 10), other tumors (10 adenocarcinomas, 2 squamous cell carcinomas and 1 malignant lymphoma), and the corresponding normal mucosa were investigated by in situ hybridization, reverse transcription-PCR (RT-PCR), real-time RT-PCR, and immunohistochemistry.
  
  
  RESULTS
  By in situ hybridization, mild to intense signals of hASH1 mRNA were detected in 9 of 10 NECs, but not in other tumors or normal mucosa, except for focally weak signals in one carcinoid tumor. RT-PCR showed strong expression of hASH1 in a small cell NEC, followed by a moderately differentiated NEC, and a carcinoid tumor, whereas it is undetectable in adenocarcinomas or normal mucosa. By real-time RT-PCR, the amounts of hASH1 mRNA in a small cell NEC were 16,600 times higher than those in adenocarcinomas and 110 times higher than those in a carcinoid tumor. Immunohistochemically, mammalian homologue of hASH1 was positive in 7 of 10 NECs but was negative in the other tumors. Pan-endocrine markers chromogranin A and synaptophysin were positive in almost all carcinoid tumors, in 4 and 7 of the 10 NECs, respectively.
  
  
  CONCLUSIONS
  These findings revealed that hASH1 is distinctly up-regulated in gastrointestinal NECs. hASH1 may be used as a more sensitive and specific marker than conventional pan-endocrine markers for clinical diagnosis of gastrointestinal NECs.
authors.affiliation: Department of Molecular Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba 260-8670, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shida
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Furuya
authors.forename: Takashi
authors.initials: T
authors.lastname: Nikaido
authors.forename: Takashi
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Koda
authors.forename: Kenji
authors.initials: K
authors.lastname: Oda
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikura
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; C065500:ASCL1 protein, human