Abstract
Purpose: BE is a recognised precursor of esophageal adenocarcinoma (EA). However, the rate of progression of BE to adenocarcinoma is very low (0.5% per year). Identification of biomarkers that predict progression to dysplasia and adenocarcinoma is important. Epidermal growth factor receptor (EGFR) is activated in EA, which in turn cross activates the proliferative Erk and the antiapoptotic Akt pathways. Prospective data regarding the expression of these biomarkers in BE are scanty. We explored the expression of EGFR, p-Akt, and p-Erk in a prospective pilot study in patients with BE and BE with dysplasia. Methods: 21 patients with BE, and 9 patients with BE with dysplasia were prospectively enrolled. Esophageal mucosal samples were obtained endoscopically in all cases. Uniform tissue processing and fixation techniques were applied. Immuno-histochemical staining for EGFR, p-Akt, and p-Erk was performed using validated techniques. Informed consent was obtained from all participating patients. Results: EGFR expression was seen in all but one BE cases; 13 (61%) had strong positive expression. 18 BE cases (90%) showed positive expression of either p-Akt or p-Erk. There were total 9 cases of BE with either low grade (7) or high grade (2) dysplasia .8 out of these 9 cases showed positive expression of p-Akt while p-Erk was expressed in all. Strong positive expression of p-Akt and p-Erk was noted in 4 and 3 cases of BE with dysplasia, respectively. Significant correlation was observed between p-Akt and p-Erk expression in the whole study cohort [Kendall's tau = 0.3591, (P= 0.0403)]. Due to the small sample size, no statistical correlation could be inferred between expression of EGFR, p-Akt, p-Erk and the presence of low or high grade dysplasia. Conclusion: Association between p-Akt and p-Erk can lead to a survival and growth advantage for the affected premalignant cells. Whether this association leads to an aggressive course in BE or if this represents a pre-dysplastic change is unknown at this time. A larger study in BE patients with the above biomarkers is warranted.Table
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