Abstract 2394: Impact of epidermal growth factor receptor (EGFR) gene intron 1 dinucleotide CA repeat polymorphism on protein expression and clinical outcome in oral cavity squamous cell carcinoma.

Abstract

Abstract Epidermal growth factor receptor (EGFR) is one of the four members of the ErbB receptor family and has been shown to play a key role in tumorigenesis of many human cancers including oral cavity squamous cell carcinoma (OSCC). Previous studies have observed a significant relationship between EGFR overexpression and poor outcomes in head and neck squamous cell carcinoma (HNSCC) including OSCC. Elevated EGFR levels have primarily been attributed to enhanced transcriptional activity, rather than amplification of the gene. Since the EGFR intron 1 polymorphic CA dinucleotide repeats has been suggested to affect EGFR transcription efficiency, the present study was designed to explore the relationship between this CA repeats polymorphism, gene copy number and protein levels in Taiwanese OSCC. A total of 194 OSCCs were examined for EGFR protein overexpression using immunohistochemistry and for copy number using a fluorescence in situ hybridization (FISH) assay. DNAs from peripheral blood of 164 OSCC patients were also available for EGFR intron 1 CA dinucleotide repeats analysis. Overexpression and increased gene copy numbers of EGFR were found in 101 (52.06%) and 59 (30.41%) cases, respectively. The length of EGFR CA repeats were not associated with EGFR protein expression (p = 0.261) while the copy number was strongly related to protein overexpression (p < 0.001). EGFR protein overexpression was associated with young age (p = 0.036), tumor differentiation (p < 0.001) and lymph node metastasis (p = 0.028). EGFR gene copy number was also associated with young age (p = 0.009), tumor cell differentiation (p = 0.002), tumor depth (p = 0.001), lymph node metastasis (p = 0.051) and bone invasion (p = 0.003). However, the length of EGFR CA repeats was not associated with clinicopathologic factors. Patients with EGFR overexpression in their tumors were found to have significant poorer disease-free survival (DFS) (p = 0.026, log-rank test) and overall survival (OS) (p = 0.019, log-rank test) than those without overexpression. Patients with CA repeats SS form (both alleles < 19 repeats) had significantly shorter DFS and OS than those with SL and LL forms (both alleles ≥ 19 repeats) (p = 0.039 and 0.018 for DFS and OS, respectively). On the other hand, the association between an increase in EGFR gene copies and DFS or OS was insignificant. In summary, our current findings confirm that EGFR protein overexpression is closely related to EGFR copy number; but, do not support the role of CA repeats as an EGFR expression regulator. On the other hand, the length of CA repeats was significantly associated with both DFS and OS. Citation Format: Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Ling-Ling Hsieh. Impact of epidermal growth factor receptor (EGFR) gene intron 1 dinucleotide CA repeat polymorphism on protein expression and clinical outcome in oral cavity squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2394. doi:10.1158/1538-7445.AM2013-2394