Persistent genetic abnormalities in Barrett's esophagus after photodynamic therapy

Background and Aims: Photodynamic therapy (PDT) is a technique for nonsurgical treatment of patients with dysplasia in Barrett's esophagus. The primary endpoint for PDT has been resolution of dysplasia. We studied the effect of PDT at the genetic level. Methods: Archival material from 3 patients who had initial improvement in dysplasia after PDT but occurrence of high-grade dysplasia during follow-up was used. Biopsy specimens were analyzed for increased proliferation, aneuploidy, p53 protein overexpression, p53 mutations, and p16 promoter hypermethylation. Results: Patients developed high-grade dysplasia 16, 28, and 37 months after PDT. In all cases, one or more genetic markers were positive after PDT treatment, whereas histology was downstaged consistently after therapy. Increasing genetic abnormalities were noted by the end of follow-up. Conclusions: Genetic abnormalities may persist after PDT despite phenotypical improvement of dysplasia. These patients may progress to high-grade dysplasia or develop adenocarcinoma. Histologic improvement in dysplasia is an inadequate endpoint for PDT in patients with Barrett's esophagus.