title: FADD expression is associated with regional and distant metastasis in squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  The Fas-associated death domain gene (FADD) is often overexpressed in squamous cell carcinoma of the head and neck (HNSCC), and is considered to be a driver gene in amplification of the chromosomal 11q13.3 region. Amplification of 11q13.3 is associated with increased metastasis in HNSCC and breast cancer. The aim of this study was to investigate the association between FADD protein expression in advanced-stage HNSCC and clinicopathological features and outcome.
  
  
  RESULTS
  Tumour tissues of 177 HNSCC patients uniformly treated with primary surgery and postoperative radiotherapy were collected. FADD expression was assessed on pretreatment tumour biopsies using immunohistochemistry. High FADD expression was detected in 44% of the HNSCC patients. High expression was associated with an increased rate of lymph node metastasis (P = 0.001) and with a shorter distant metastasis-free interval (DMFI) (HR 2.6, 95% CI 1.0-6.7, P = 0.046) when lymph node metastases were present.
  
  
  CONCLUSIONS
  Our data show that an increase in FADD expression is associated with a higher incidence of lymph node metastasis at presentation, and with shorter DMFI when lymph node metastases are present. High FADD expression in the primary tumour could be a useful marker to select patients for systemic treatment strategies that reduce the risk of distant metastases.
authors.affiliation: Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Pattje
authors.forename: L J
authors.initials: LJ
authors.lastname: Melchers
authors.forename: L
authors.initials: L
authors.lastname: Slagter-Menkema
authors.forename: M F
authors.initials: MF
authors.lastname: Mastik
authors.forename: M L
authors.initials: ML
authors.lastname: Schrijvers
authors.forename: J H
authors.initials: JH
authors.lastname: Gibcus
authors.forename: P M
authors.initials: PM
authors.lastname: Kluin
authors.forename: O
authors.initials: O
authors.lastname: Hoegen-Chouvalova
authors.forename: B F A M
authors.initials: BF
authors.lastname: van der Laan
authors.forename: J L N
authors.initials: JL
authors.lastname: Roodenburg
authors.forename: J E
authors.initials: JE
authors.lastname: van der Wal
authors.forename: E
authors.initials: E
authors.lastname: Schuuring
authors.forename: J A
authors.initials: JA
authors.lastname: Langendijk
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D015331:Cohort Studies; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein
keywords: FADD; distant metastasis; head and neck neoplasms; lymphatic metastasis