Department of Radiation Oncology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Histopathology. 2013 Aug;63(2):263-70. doi: 10.1111/his.12174. Epub 2013 Jun 13.
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.
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.
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.
Fas 相关死亡结构域基因(FADD)在头颈部鳞状细胞癌(HNSCC)中常过度表达,被认为是扩增染色体 11q13.3 区域的驱动基因。11q13.3 的扩增与 HNSCC 和乳腺癌的转移增加有关。本研究旨在探讨晚期 HNSCC 中 FADD 蛋白表达与临床病理特征和预后的关系。
收集了 177 例经根治性手术和术后放疗统一治疗的 HNSCC 患者的肿瘤组织。采用免疫组织化学法检测术前肿瘤活检组织中的 FADD 表达。在 44%的 HNSCC 患者中检测到 FADD 高表达。高表达与淋巴结转移率增加(P = 0.001)和存在淋巴结转移时的无远处转移间隔时间(DMFI)缩短(HR 2.6,95%CI 1.0-6.7,P = 0.046)相关。
我们的数据表明,FADD 表达增加与首发时淋巴结转移的发生率增加有关,并且当存在淋巴结转移时,DMFI 更短。原发肿瘤中 FADD 高表达可能是选择患者进行全身治疗策略的有用标志物,这些策略可以降低远处转移的风险。