title: Clinicopathologic and immunohistochemical characteristics of gastric adenocarcinoma with enteroblastic differentiation: a study of 29 cases.
abstract: BACKGROUND
  Gastric adenocarcinoma with enteroblastic differentiation (GAED) has been recognized as a variant of alpha-fetoprotein (AFP)-producing gastric carcinoma, although its clinicopathologic and immunohistochemical features have not been fully elucidated.
  
  
  METHODS
  To elucidate the clinicopathologic and immunohistochemical features of GAED, we analyzed 29 cases of GAED, including ten early and 19 advanced lesions, and compared these cases with 100 cases of conventional gastric adenocarcinoma (CGA). Immunohistochemistry for AFP, glypican 3, SALL4, and p53 was performed, and the phenotypic expression of the tumors was evaluated by immunostaining with antibodies against MUC5AC, MUC6, MUC2, CD10, and caudal-type homeobox 2 (CDX2).
  
  
  RESULTS
  Lymphatic and venous invasion was more frequent in GAED (76 and 72 %) than in CGA (41 and 31 %; P ≤ 0.001). Lymph node metastasis was more frequently observed in GAED (69 %) than in CGA (38 %; P = 0.005), as were synchronous or metachronous liver metastases (GAED, 31 %; CGA, 6 %; P ≤ 0.001). Immunohistochemically, all GAED were positive for at least one of three enteroblastic linage markers (AFP, glypican 3, and SALL4). Glypican 3 was the most sensitive marker (83 %) for GAED, followed by SALL4 (72 %) and AFP (45 %), whereas no CGA was positive. Furthermore, the rate of positive p53 staining was 59 % in GAED. Regarding the mucin phenotype, CD10 and CDX2 were diffusely or focally expressed in all GAED cases. Invasive areas with hepatoid or enteroblastic differentiation were negative for CD10 and CDX2.
  
  
  CONCLUSIONS
  Clinicopathologic features of GAED differ from those of CGA. GAED shows aggressive biological behavior, and is characteristically immunoreactive to AFP, glypican 3, or SALL4.
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. t-murakm@juntendo.ac.jp.|Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. t-murakm@juntendo.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
authors.affiliation: Department of Surgical and Molecular Pathology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mitomi
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Ueyama
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Osada
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Nagahara
authors.affiliation: Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality* / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism*; D000071616:CDX2 Transcription Factor / Q000276:immunology / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D053673:Glypicans / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000276:immunology / Q000378:metabolism; D055272:Mucin-6 / Q000276:immunology / Q000378:metabolism; D013274:Stomach Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology*; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000276:immunology / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000276:immunology / Q000378:metabolism
chemical_list: C097353:AFP protein, human; D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C105937:GPC3 protein, human; D053673:Glypicans; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D055271:Mucin 5AC; D055272:Mucin-6; C472575:SALL4 protein, human; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000509:alpha-Fetoproteins
keywords: Alpha-fetoptotein-producing gastric carcinoma; Gastric adenocarcinoma with enteroblastic differentiation; Glypican-3; SALL4