Tetsuo Ushiku1,2,3, Hiroshi Uozaki1,2,3, Aya Shinozaki‐Ushiku1,2,3, Satoshi Ota1,2,3, Keisuke Matsuzaka1,2,3, Sachiyo Nomura1,2,3, Michio Kaminishi1,2,3, Hiroyuki Aburatani1,2,3, Tatsuhiko Kodama1,2,3, Masashi Fukayama1,2,3
13Department of Surgery, Showa General Hospital
24Genome Science Division, Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, Japan
3Departments of 1Pathology and Diagnostic Pathology, 2Surgery, Graduate School of Medicine, University of Tokyo
Tóm tắt
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 α‐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 α‐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 α‐fetoprotein‐producing GC. GPC3 is expected to be a target of forthcoming immunotherapy for a patient bearing this specific type of GC. (Cancer Sci 2009; 100: 626–632)
