title: The extrinsic apoptotic signaling pathway in gastric adenocarcinomas assessed by tissue microarray.
abstract: The purpose of this investigation was to analyze the immunoexpression of FasL, Fas, FADD, cleaved caspase 8, and cleaved caspase 3 in gastric cancer. Formalin-fixed and paraffin-embedded gastric adenocarcinoma tissues from 87 patients, including adjacent normal tissues, were included on tissue microarray by immunohistochemistry. The tumor and the adjacent normal tissues were positive for FasL in 66.7% and 90.6%, for Fas in 52.8% and 52.4%, for FADD in 67.4% and 82.3%, for cleaved caspase 8 in 27.9% and 37.7%, and for cleaved caspase 3 in 33.7% and 8.3%, respectively. FasL and the FADD from tumor were statistically different in relation to the histological type. Cleaved caspase 8 was statistically different in relation to clinical stage (p=0.031). The FADD from normal tissue was statistically different in relation to age (p=0.039), sex (p=0.055), clinical stage (p=0.019), and Fas was different in relation to tumor size (p=0.012). In the tumor, we observed a correlation between FasL and Fas, FasL and FADD, and FasL and cleaved caspase 3. In the adjacent normal tissue, a correlation was observed between FasL and Fas, FasL and FADD. There was no association of another marker with sex, age, clinical stage, and survival. Our results suggest that these proteins mediate the early extrinsic apoptotic pathway in gastric cancer and adjacent normal mucosa. FasL protein binds to Fas protein and subsequently binds to death receptor FADD signaling activation of the extrinsic apoptotic pathway. In this phase, there was inhibition of caspase 8 and, consequently, decreased apoptosis.
authors.affiliation: Departamento de Patologia, Universidade Federal de São Paulo, UNIFESP, SP, Brazil.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Gomes
authors.forename: Celina T F
authors.initials: CT
authors.lastname: Oshima
authors.forename: Helena R C
authors.initials: HR
authors.lastname: Segreto
authors.forename: Luis M
authors.initials: LM
authors.lastname: Barrazueta
authors.forename: Henrique O
authors.initials: HO
authors.lastname: Costa
authors.forename: Flavio O
authors.initials: FO
authors.lastname: Lima
authors.forename: Nora M
authors.initials: NM
authors.lastname: Forones
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Ribeiro
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000032:analysis; D053181:Caspase 8 / Q000032:analysis; D053222:Fas Ligand Protein / Q000032:analysis; D053200:Fas-Associated Death Domain Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015398:Signal Transduction / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D046888:Tissue Array Analysis; D019014:fas Receptor / Q000032:analysis
chemical_list: C505533:FADD protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D019014:fas Receptor; D053148:Caspase 3; D053181:Caspase 8