Abstract 3855: Clinical implications of FADD copy number gain/amplification and high protein expression in areca-quid-associated oral cavity squamous cell carcinomas

Abstract

Abstract Gene amplification provides a means for overexpression of cell growth promoting genes driving tumor formation and progression. Indeed, cancer genomic analyses have indicated that gene amplification occurs somatically in certain regions of human cancer genome. Among them, amplification of the 11q13.3 is a frequent event in human cancers including head and neck squamous cell carcinoma. Our whole genome copy number alterations (CNAs) study also revealed amplification of 11q13.3 in oral cavity squamous cell carcinoma (OSCC) in Taiwan. This region contains at least 5 cancer-related genes including CCND1 and FADD. CCND1 amplification has been demonstrated as an oncogenic driver gene in breast, bladder, head and neck, liver and lung squamous cancer. FADD, an apoptotic effector, was previously identified as a novel cancer driver gene in laryngeal/pharyngeal cancer. It is warranting for further investigation to determine whether FADD amplification is also a cancer driver in other types of human cancer. Therefore, this study was designed to explore whether FADD is a cancer driver in Taiwanese OSCC based on CNAs, protein expression and their clinical implications. A total of 346 male OSCCs were examined for gene copy number using TaqMan CNV analysis and protein expression using immunohistochemistry. We found that the intensity of FADD protein expression was strongly correlated with gene copy number gain/amplification. Gene copy number gain/amplification and high protein expression was observed in 70 (20.23%) and 199 (57.51%) OSCCs, respectively. Both FADD gene copy number gain/amplification and high protein expression were significantly associated with lymph node metastasis (p<0.001). The frequency of FADD high protein expression was associated with young age at diagnosis and high grade tumor differentiation. Furthermore, FADD copy number gain/amplification and high protein expression was associated with poor disease-free and overall survival. Patients with both FADD copy number gain/amplification and high protein expression had the lowest disease-free and overall survival. After adjusting primary tumor status, tumor differentiation, lymph node metastasis and age at diagnosis, disease-free survival was still significantly decreased in patients with either copy number gain/amplification or high protein expression. In conclusion, our data revealed that FADD can be considered as a potential driver gene in OSCCs in Taiwan. Citation Format: Chia-Jung Liao, Huei-Tzu Chien, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Ling-Ling Hsieh. Clinical implications of FADD copy number gain/amplification and high protein expression in areca-quid-associated oral cavity squamous cell carcinomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3855. doi:10.1158/1538-7445.AM2015-3855