title: Transcriptional factor typing with SOX2, HNF4aP1, and CDX2 closely relates to tumor invasion and Epstein-Barr virus status in gastric cancer.
abstract: BACKGROUND
  Gastric cancer (GC) is a major cancer, sometimes associated with Epstein-Barr virus (EBV). Some transcriptional factors (TFs) are specific to the digestive tract and related to the character of the tumors.
  
  
  METHODS
  We studied three TFs, SOX2, CDX2, and hepatocyte nuclear factor 4 alpha-promoter 1 (HNF4aP1) in GC. First, 255 tumors including 31 EBV-associated GC were immunohistochemically examined using tissue arrays and compared TF type and mucin phenotype. We classified them into 4 TF types: N-TF type as SOX2-/HNF4aP1- tumor, G: SOX2+/HNF4aP1-, GI: SOX2+/HNF4aP1+, and I: SOX2-/HNF4aP1+. Next, 915 GCs were intensely investigated and compared with their clinicopathological factors.
  
  
  RESULTS
  In the first study, 255 GCs were classified into N-TF 44%, G-TF 31%, GI-TF 3%, and I-TF 2%. The TF type did not strictly accord with the mucin phenotype, classified by MUC2/5AC/6/CD10 expression. EBV status was the only factor related to both the TF and mucin phenotype classifications (P<0.0001, <0.0001). TF classification is related to more factors including tumor stage, than mucin phenotype classification. The second study using 915 GCs revealed that N-TF gradually increased and I-TF decreased as GC invaded deeper. TF classification was not related to nodal involvement in each tumor stage. HNF4aP1 and CDX2 were independent factors for early stage tumor in logistic regression analysis.
  
  
  CONCLUSIONS
  EBV-associated GC is a discriminating group in both TF and mucin phenotype. TF classification, especially the absence of HNF4aP1 and CDX2, is related to tumor invasion. TF classification is a useful marker to study the carcinogenesis of GC further.
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. uozaki-tky@umin.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.forename: Rita Rani
authors.initials: RR
authors.lastname: Barua
authors.forename: Sun
authors.initials: S
authors.lastname: Minhua
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ushiku
authors.forename: Rumi
authors.initials: R
authors.lastname: Hino
authors.forename: Aya
authors.initials: A
authors.lastname: Shinozaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D000368:Aged; D000704:Analysis of Variance; D000071616:CDX2 Transcription Factor; D020031:Epstein-Barr Virus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D018398:Homeodomain Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors