title: Glypican 3-expressing gastric carcinoma: distinct subgroup unifying hepatoid, clear-cell, and alpha-fetoprotein-producing gastric carcinomas.
abstract: Gypican-3 (GPC3) has been recognized as an oncofetal protein in hepatic neoplasms and yolk sac tumors. To characterize a distinct subgroup of gastric carcinoma (GC) expressing GPC3 (GPC3-GC), primary and metastatic GC tissues were evaluated by immunohistochemistry with special focus on their related entities: hepatoid, clear-cell, and alpha-fetoprotein-producing GC. GPC3-GC was defined as focal GPC3-GC when 10-49% of neoplastic cells were positive, and as diffuse GPC3-GC when more than 50% of cells were positive. Among 926 GC cases, 101 (11%) were GPC3-GC, of which 45 were diffuse and 56 were focal GPC3-GC. Specific histological patterns, such as the hepatoid and clear-cell patterns, were frequently observed in diffuse GPC3-GC (38 and 49%, respectively) and in focal GPC3-GC (4 and 25%, respectively), whereas these patterns were extremely rare in GPC3-negative GC. Immunoreactive alpha-fetoprotein was only identified in GPC3-GC (38% of diffuse and 14% of focal GPC3-GC). Both diffuse and focal GPC3-GC showed nodal metastasis more frequently (67 and 55%, respectively) than GPC3-negative GC (34%), and the diffuse GPC3-GC had significantly more T2-4 and M1 stage cases. GPC3 immunostaining was present in 57 out of 61 nodal metastases (93%) and in all four liver metastases examined. Importantly, diffuse GPC3 expression was observed in the liver metastasis, even if the primary tumor was focal GPC3-GC. GPC3-GC is a distinctive group of GC, which unifies hepatoid, clear-cell, and alpha-fetoprotein-producing GC. GPC3 is expected to be a target of forthcoming immunotherapy for a patient bearing this specific type of GC.
authors.affiliation: Department of Pathology and Diagnostic Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ushiku
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.forename: Aya
authors.initials: A
authors.lastname: Shinozaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ota
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsuzaka
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Nomura
authors.forename: Michio
authors.initials: M
authors.lastname: Kaminishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D053673:Glypicans / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism; D008207:Lymphatic Metastasis; D008954:Models, Biological; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D053673:Glypicans; D000509:alpha-Fetoproteins