Epidermal Growth Factor Receptor Mutations In Esophageal Adenocarcinoma And Barrett's Esophagus

BackgroundEsophageal adenocarcinoma (EAC) is frequently accompanied by Barrett's esophagus (BE), one of the most common premalignant lesions. Specific activating mutations of epidermal growth factor receptor (EGFR) were identified in a subset of non-small-cell lung cancer (NSCLC) with dramatic sensitivity to the tyrosine kinase inhibitors (TKI), and mutation specific antibodies could detect the status of the EGFR mutations. In this study, we used immunohistochemistry (IHC) with EGFR mutation specific antibodies to detect if the mutations exist at the lesions of EAC and BE.Experimental designIHC staining was performed on 105 paraffin embedded samples of EAC and BE, as well as 30 samples of esophageal squamous cell carcinoma (ESCC) using antibodies against total EGFR and mutant EGFR to determine the prevalence of EGFR mutations in these cancers and to acquire the knowledge on the genetic and molecular alterations along the esophageal metaplasia-dysplasia-carcinoma sequence. The DNA from the samples stained positive by mutant specific antibodies was extracted for direct DNA sequencing.Results11 of the 105 EAC and BC specimens were positively stained by EGFR mutation specific antibody. In these positive staining cases,6 were exon 19 deletion and 5 were L858R substitution mutation. The percentage of positive staining is 10.5%. No EGFR mutation was found from 30 ESCC samples.Conclusion1 Activating EGFR mutations present in a subset of EAC and BE.2 It may play an important role as an early event in the tumor transformation.3 A clinical trial will be helpful to assess if it can be used as a predictive biomarker for the risk assessment in the development of dysplasia changes and the progression to EAC and for the selection of EAC patients in target therapy.