title: Expression of nuclear and cytoplasmic phosphorylated FADD in gastric cancers.
abstract: Fas-associated death domain (FADD) plays a crucial role during death receptor-mediated apoptosis. In addition, FADD possesses apoptosis-independent activities, including cell-cycle regulation and cell proliferation regulated by the phosphorylation of FADD at Ser194. The aim of this study was to explore the possibility whether alteration of phosphorylated FADD (p-FADD) expression might be a characteristic of gastric cancer. We analyzed the expression of p-FADD protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. In the normal gastric mucosal cells, surface and glandular epithelial cells evenly expressed p-FADD in the nuclei but not in the cytoplasm. In the cancers, p-FADD expression was detected in 38 cases (63%) of the gastric carcinomas, but there was no p-FADD immunostaining in the remaining 22 cancers (37%). Of note, p-FADD immunostaining was observed in cytoplasm/nuclei (20 cancers; 33%) and cytoplasm (18 cancers; 30%). There was no significant association of p-FADD expression with clinocopathological characteristics, including invasion, metastasis, and stage. Our data showed that the expression of p-FADD in gastric cancers was heterogenous in its location compared to the uniform nuclear expression of p-FADD in normal gastric cells. Many of the cancers (67%) were devoid of nuclear p-FADD, suggesting that p-FADD functions in the nucleus may be perturbed in the cancers. Also, p-FADD expression in the cytoplasm in a large fraction of the cancers (63%), not seen in the normal cells, suggested that the cell death functions of p-FADD could be altered in the cancer cells.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.
authors.forename: Nam Jin
authors.initials: NJ
authors.lastname: Yoo
authors.forename: Sung Hak
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun Goo
authors.initials: EG
authors.lastname: Jeong
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Young Hwa
authors.initials: YH
authors.lastname: Soung
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.forename: Sang Ho
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Sug Hyung
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D014408:Biomarkers, Tumor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism* / Q000473:pathology; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D005753:Gastric Mucosa / Q000033:anatomy & histology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010766:Phosphorylation; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein