Abstract 1082: The amplification and overexpression of the calcium activated chloride channel TMEM16A (aka DOG1) has a prognostic role in patients with head and neck squamous cell carcinoma

Abstract

Abstract Introduction: The calcium activated chloride channel TMEM16A, which is also known as DOG1, is used as a sensitive marker for the diagnosis of gastrointestinal tumors (GIST). Its expression has also been described in head and neck squamous cell carcinomas (HNSCC) and in esophageal SCC. Surprisingly, until recently (2008) its role as chloride channel was not known. The TMEM16A gene is localized very close to the Cyclin D1 gene (CCND1), which is a putative target gene of the 11q13 amplicon. Aim of this study was the analysis of the genomic and expression status of TMEM16A in HNSCC. Methods: We applied fluorescence in-situ hybridization (FISH) and immunohistochemistry to a tissue microarray (TMA) containing tissue specimens from 216 primary tumors from the oral cavity, 40 local recurrences and 76 neck dissections. We validated our results on a second cohort consisting of additional 158 HNSCCs. In order to analyze the prognostic role of TMEM16A, a subset of 365 primary tumors with complete follow-up data was selected. Results: We found genomic amplification of the TMEM16A gene in 13% of the primary head and neck squamous cell carcinomas and in 12% of the local recurrences. Although the prevalence of TMEM16A protein expression was lower (8%), a strong correlation between TMEM16A amplification and overexpression was found (p<0.0001). FISH analysis of Cyclin D1 (CCND1) revealed co-amplification of these two genes (p<0.0001). Interestingly, both, genomic amplification and expression of TMEM16A identified a subgroup of HNSCC patients with poor survival (p<0.05). Conclusions: TMEM16A positivity characterizes a small subgroup of HNSCC with poor survival. The strong correlation between genomic amplification and expression suggests that TMEM16A is one of the driving genes of the 11q13 amplicon in HNSCC. Additional studies may show how this chloride channel can be used as a therapeutic target in patients with TMEM16A positive tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1082. doi:10.1158/1538-7445.AM2011-1082