Abstract 2696: EGFR intron-1 CA repeat polymorphism is a predictor of outcome in complete resected only surgically treated esophageal cancer
Authors: Yogesh K. Vashist, Emre F. Yekebas, Katharina Effenberger, Florian Trump, Florian Gebauer, Viacheslav Kalinin, Burkhard Brandt, Klaus Pantel, Jakob R. Izbicki
Journal: Cancer Research (2010)

Abstract Background: Basal transcription regulation of the epidermal growth factor receptor (EGFR) is dependent upon a CA simple sequence repeat polymorphism in the intron-1. Here, we evaluate the role of CA repeat polymorphism in intron-1 as a prognostic marker in only surgically (no neoadjuvant or adjuvant treatment) complete resected esophageal cancer patients. Methods: Genomic DNA was extracted from peripheral blood leucocytes of 241 patients preoperatively. To determine the number of the CA repeats in the intron-1 DNA was amplified by polymerase chain reaction and sequenced. The results were correlated with clinicopathological parameters and clinical outcome. Results: Three genotypes were defined based on cut-off points for short allele (S) with ≤18 and long allele (L) &amp;gt;18 CA repeats. A steadily increasing risk was evident between LL, SL and SS genotype for larger tumor size, presence of lymph node metastases and disseminated tumor cells in bone marrow as well as tumor recurrence (P &amp;lt; 0.001 each, chi-square test). A gradual decrease in disease-free and overall survival was present between LL, SL and SS patients (P &amp;lt; 0.001 each, log rank test). The median disease-free survival in LL patients was 37.5 months (95% confidence interval (95%CI) 31.2 to 43.8 months), in SL patients 10.0 months (95%CI 7.9 to 12.1 months) and in SS patients only 6.0 months (95%CI 5.4 to 6.6 months). Accordingly, the median overall survival was only 11.6 months (95%CI 9.1 to 14.2 months) in SS patients compared to 17.2 months (95%CI 14.7 to 19.8 months) in SL and 55.0 months (95%CI 41.9 to 68.0 months) in LL patients. The different clinical outcomes in CA genotypes were also evident in nodal status and histological subtype adjusted subgroup analyses. The CA repeat polymorphism in intron-1 was identified as the strongest independent prognosticator of tumor recurrence and survival (Cox regression analyses). The hazard ratio for tumor recurrence in SL patients was 2.3 (95%CI 1.4 to 3.8, P = 0.001) and 6.0 (95%CI 3.3 to 10.8, P &amp;lt; 0.001) in SS patients compared to LL patients. The hazard ratio for overall survival in SL patients was 3.3 (95%CI 1.9 to 5.4, P &amp;lt; 0.001) and 6.5 (95%CI 3.6 to 11.6, P &amp;lt; 0.001) in SS patients compared to LL patients. Conclusions/Significance: The CA repeat polymorphism in the intron-1 is a strong prognostic factor for tumor recurrence and overall survival in patients with complete resected and only surgically treated esophageal cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2696.