title: Phosphorylated FADD is not prognostic for local control in T1-T2 supraglottic laryngeal carcinoma treated with radiotherapy.
abstract: The Fas-Associated Death Domain (FADD) gene is located in the chromosome 11q13-region and frequently is amplified in head and neck squamous cell carcinoma. Expression of FADD and its phosphorylated isoform (pFADD) have been associated with aggressive tumor growth, lymph node metastasis, and overall survival. Previously, we demonstrated that pFADD expression was related to a significantly improved local control in early stage (tumor [T]1 to T2) glottic laryngeal squamous cell carcinoma (LSCC). The aim of this study was to examine the prognostic value of pFADD and FADD in T1 to T2 supraglottic LSCC treated with primarily radiotherapy.
  
  
  
  Tumor tissue sections of 60 patients with T1 to T2 supraglottic LSCC treated with primarily radiotherapy were assessed immunohistochemically for expression of pFADD and FADD. Expression percentages and clinical parameters and their associations with clinical outcome were studied using Cox regression and Kaplan-Meier survival analyses. Expression percentages in supraglottic and glottic LSCC were compared using the Mann-Whitney U test.
  
  
  
  Expression of pFADD and FADD in supraglottic and glottic LSCC did not significantly differ. In supraglottic LSCC, both pFADD and FADD did not show prognostic value for local control (hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.98-1.03; HR 1.03, 95% CI 0.60-1.78, respectively) and overall survival (HR 0.99, 95% CI 0.98-1.01; HR 1.19, 95% CI 0.83-1.71 respectively). In this cohort, lymph node status was the best predictor for local control (HR 3.73, 95% CI 1.30-10.67).
  
  
  
  In this homogeneous cohort of T1 to T2 supraglottic LSCC primarily treated with radiotherapy, lymph node status was associated with local recurrence, whereas the expression of pFADD was not.
  
  
  
  NA. Laryngoscope, 127:E301-E307, 2017.
authors.affiliation: Department of Pathology and Medical Biology.|Department of Otorhinolaryngology and Head and Neck Surgery.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Wachters
authors.affiliation: Department of Pathology and Medical Biology.|Department of Otorhinolaryngology and Head and Neck Surgery.
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Schrijvers
authors.affiliation: Department of Pathology and Medical Biology.
authors.forename: Lorian
authors.initials: L
authors.lastname: Slagter-Menkema
authors.affiliation: Department of Pathology and Medical Biology.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Mastik
authors.affiliation: Department of Radiation Oncology.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.affiliation: Department of Epidemiology.
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.affiliation: Department of Oral and Maxillofacial Surgery , University Medical Center Groningen, University of Groningen.
authors.forename: Jan L
authors.initials: JL
authors.lastname: Roodenburg
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery.
authors.forename: Bernard F A M
authors.initials: BFAM
authors.lastname: van der Laan
authors.affiliation: Department of Pathology and Medical Biology.|Department of Department of Pathology, Martini Hospital, Groningen, The Netherlands.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: van der Wal
authors.affiliation: Department of Pathology and Medical Biology.
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D005260:Female; D005931:Glottis / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000378:metabolism; D012044:Regression Analysis; D018709:Statistics, Nonparametric
chemical_list: D014408:Biomarkers, Tumor; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D020033:Protein Isoforms
keywords: FADD; head and neck squamous cell carcinoma; laryngeal squamous cell carcinoma; local control; overall survival; pFADD; radiotherapy