title: Increased expression of FLIP, an inhibitor of Fas-mediated apoptosis, in stomach cancer.
abstract: Despite the cell surface expression of Fas (Apo-1/CD95), many types of tumor cells, including stomach cancer cells, are resistant to Fas-mediated apoptosis, indicating the presence of inactivating mechanisms of Fas signaling. Expression of FLICE-like inhibitory protein (FLIP), one of the inhibitory proteins of Fas-mediated apoptosis, has been reported in several cancer types, but not in stomach cancer. In the present study, we analyzed the expression of Fas and FLIP in 60 advanced gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. Immunopositivity (defined as >/=30% of the neoplastic cells) was observed for Fas in 58 (97%) and FLIP in 54 (90%) of the 60 cancers. All of the tumors with FLIP immunostaining also showed Fas immunostaining. Loss of cell surface Fas immunostaining, another mechanism of Fas resistance, was observed in 45 tumors (75%). By contrast, normal gastric mucosal cells showed no or weak expression of both Fas and FLIP. Taken together, these results indicate that increased expression of FLIP is a frequent event in stomach carcinomas, and suggest that for evading apoptosis stomach carcinoma cells in vivo may need FLIP expression, which might contribute to tumor development.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
authors.forename: Hong Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Su Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D020411:Oligonucleotide Array Sequence Analysis; D013274:Stomach Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology*; D019014:fas Receptor / Q000032:analysis*
chemical_list: D015703:Antigens, CD; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019014:fas Receptor