title: Clinical Implications of FADD Gene Amplification and Protein Overexpression in Taiwanese Oral Cavity Squamous Cell Carcinomas.
abstract: Amplification of 11q13.3 is a frequent event in human cancers, including head and neck squamous cell carcinoma. This chromosome region contains several genes that are potentially cancer drivers, including FADD (Fas associated via death domain), an apoptotic effector that was previously identified as a novel oncogene in laryngeal/pharyngeal cancer. This study was designed to explore the role of FADD in oral squamous cell carcinomas (OSCCs) samples from Taiwanese patients, by assessing copy number variations (CNVs) and protein expression and the clinical implications of these factors in 339 male OSCCs. The intensity of FADD protein expression, as determined by immunohistochemistry, was strongly correlated with gene copy number amplification, as analyzed using a TaqMan CNV assay. Both FADD gene copy number amplification and high protein expression were significantly associated with lymph node metastasis (P < 0.001). Patients with both FADD copy number amplification and high protein expression had the shortest disease-free survival (DFS; P = 0.074 and P = 0.002) and overall survival (OS; P = 0.011 and P = 0.027). After adjusting for primary tumor status, tumor differentiation, lymph node metastasis and age at diagnosis, DFS was still significantly lower in patients with either copy number amplification or high protein expression (hazard ratio [H.R.] = 1.483; 95% confidence interval [C.I.], 1.044-2.106). In conclusion, our data reveal that FADD gene copy number and protein expression can be considered potential prognostic markers and are closely associated with lymph node metastasis in patients with OSCC in Taiwan.
authors.affiliation: Department of Public Health, Chang Gung University, Tao-Yuan, Taiwan, R.O.C.
authors.forename: Huei-Tzu
authors.initials: HT
authors.lastname: Chien
authors.affiliation: Department of Anatomy, Chang Gung University, Tao-Yuan, Taiwan, R.O.C.
authors.forename: Sou-De
authors.initials: SD
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, R.O.C.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Chuang
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial, Tao-Yuan, Taiwan, R.O.C.|Taipei CGMH Head and Neck Oncology Group, Tao-Yuan, Taiwan, R.O.C.
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, R.O.C.|Taipei CGMH Head and Neck Oncology Group, Tao-Yuan, Taiwan, R.O.C.
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Department of Public Health, Chang Gung University, Tao-Yuan, Taiwan, R.O.C.|Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial, Tao-Yuan, Taiwan, R.O.C.|Taipei CGMH Head and Neck Oncology Group, Tao-Yuan, Taiwan, R.O.C.
authors.forename: Shiang-Fu
authors.initials: SF
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D056915:DNA Copy Number Variations; D018572:Disease-Free Survival; D053200:Fas-Associated Death Domain Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D013624:Taiwan
chemical_list: D014408:Biomarkers, Tumor; D053200:Fas-Associated Death Domain Protein