Phosphorylated FADD is not prognostic for local control in T1-T2 supraglottic laryngeal carcinoma treated with radiotherapy

Abstract

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.

Keywords: FADD; head and neck squamous cell carcinoma; laryngeal squamous cell carcinoma; local control; overall survival; pFADD; radiotherapy.