Abstract
This study was designed to explore the relationship between epidermal growth factor receptor (EGFR) CA repeats polymorphism and protein expression in oral cavity squamous cell carcinoma (OSCC). A total of 194 OSCCs were examined for EGFR protein overexpression, gene copy number and the length of their CA repeats. The length of the EGFR CA repeats was found not to be associated with EGFR gene copy number or with protein overexpression. To exclude the effect of EGFR gene copy number on protein overexpression, only those OSCC tumors with disomy of the EGFR gene were included in further analysis. In this subgroup, EGFR protein overexpression was significantly associated with poor differentiation of the tumor cells and lymph node metastasis, especially extra-capsular spread. However, EGFR CA repeats were not related to any clinicopathological factor. Interestingly, patients genetically found to have the EGFR CA repeats SS genotype and having tumors with EGFR protein overexpression were found to have a worst prognosis in terms of disease-free survival (DFS) (HR = 2.68; 95% CI, 1.03–6.98) after multivariate adjustment. The present study demonstrates that concurrent overexpression of EGFR protein in the presence genetically of the SS form CA repeats acts as a predictor for poor DFS.
Highlights
In Taiwan, oral cancer is the fourth most common cancer in men[1]
We have previously shown that epidermal growth factor receptor (EGFR) genetic mutations play a very minor role in oral cavity squamous cell carcinoma (OSCC), whereas gene copy number was found to be significantly correlated with EGFR protein overexpression[4]
We comprehensively investigated the effects of EGFR CA repeat genotype on OSCC risk and protein overexpression, as well as evaluating its prognostic role
Summary
In Taiwan, oral cancer (including sub-sites in the oral cavity, oropharynx and hypopharynx) is the fourth most common cancer in men[1]. Etienne-Grimaldi et al.[9] have reported that the number of CA repeats is inversely correlated with protein expression in human tumors, including head and neck cancer. To confirm that the number of CA repeats had a significant influence on EGFR expression in a later study[10] This contradictory result may be mainly due to the complexity of head and neck cancer, which is composed of cancers from a number of different anatomical sites. We have previously shown that EGFR genetic mutations play a very minor role in OSCCs, whereas gene copy number was found to be significantly correlated with EGFR protein overexpression[4]. We comprehensively investigated the effects of EGFR CA repeat genotype on OSCC risk and protein overexpression, as well as evaluating its prognostic role
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