PMID- 28304089 OWN - NLM STAT- MEDLINE DCOM- 20170915 LR - 20220410 IS - 1531-4995 (Electronic) IS - 0023-852X (Linking) VI - 127 IP - 9 DP - 2017 Sep TI - Phosphorylated FADD is not prognostic for local control in T1-T2 supraglottic laryngeal carcinoma treated with radiotherapy. PG - E301-E307 LID - 10.1002/lary.26563 [doi] AB - OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E301-E307, 2017. CI - (c) 2017 The American Laryngological, Rhinological and Otological Society, Inc. FAU - Wachters, Jan E AU - Wachters JE AD - Department of Pathology and Medical Biology. AD - Department of Otorhinolaryngology and Head and Neck Surgery. FAU - Schrijvers, Michiel L AU - Schrijvers ML AD - Department of Pathology and Medical Biology. AD - Department of Otorhinolaryngology and Head and Neck Surgery. FAU - Slagter-Menkema, Lorian AU - Slagter-Menkema L AD - Department of Pathology and Medical Biology. FAU - Mastik, Mirjam AU - Mastik M AD - Department of Pathology and Medical Biology. FAU - Langendijk, Johannes A AU - Langendijk JA AD - Department of Radiation Oncology. FAU - de Bock, Geertruida H AU - de Bock GH AD - Department of Epidemiology. FAU - Roodenburg, Jan L AU - Roodenburg JL AD - Department of Oral and Maxillofacial Surgery , University Medical Center Groningen, University of Groningen. FAU - van der Laan, Bernard F A M AU - van der Laan BFAM AD - Department of Otorhinolaryngology and Head and Neck Surgery. FAU - van der Wal, Jacqueline E AU - van der Wal JE AD - Department of Pathology and Medical Biology. AD - Department of Department of Pathology, Martini Hospital, Groningen, The Netherlands. FAU - Schuuring, Ed AU - Schuuring E AD - Department of Pathology and Medical Biology. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170317 PL - United States TA - Laryngoscope JT - The Laryngoscope JID - 8607378 RN - 0 (Biomarkers, Tumor) RN - 0 (FADD protein, human) RN - 0 (Fas-Associated Death Domain Protein) RN - 0 (Protein Isoforms) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/genetics MH - Carcinoma, Squamous Cell/*genetics/pathology/radiotherapy MH - Fas-Associated Death Domain Protein/*metabolism MH - Female MH - Glottis/pathology MH - Humans MH - Kaplan-Meier Estimate MH - Laryngeal Neoplasms/*genetics/pathology/radiotherapy MH - Lymph Nodes/pathology MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/*genetics/pathology/radiotherapy MH - Phosphorylation MH - Prognosis MH - Proportional Hazards Models MH - Protein Isoforms/metabolism MH - Regression Analysis MH - Statistics, Nonparametric OTO - NOTNLM OT - FADD OT - head and neck squamous cell carcinoma OT - laryngeal squamous cell carcinoma OT - local control OT - overall survival OT - pFADD OT - radiotherapy EDAT- 2017/03/18 06:00 MHDA- 2017/09/16 06:00 CRDT- 2017/03/18 06:00 PHST- 2016/08/18 00:00 [received] PHST- 2017/01/16 00:00 [revised] PHST- 2017/02/06 00:00 [accepted] PHST- 2017/03/18 06:00 [pubmed] PHST- 2017/09/16 06:00 [medline] PHST- 2017/03/18 06:00 [entrez] AID - 10.1002/lary.26563 [doi] PST - ppublish SO - Laryngoscope. 2017 Sep;127(9):E301-E307. doi: 10.1002/lary.26563. Epub 2017 Mar 17.