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Buried Barrett's Epithelium Following Photodynamic Therapy Shows Reduced Crypt Proliferation and Absence of DNA Content Abnormalities

Hornick, Jason L., M.D., Ph.D.1; Mino-Kenudson, Mari, M.D.2; Lauwers, Gregory Y., M.D.2; Liu, Weitian, M.D., Ph.D.3; Goyal, Raj, M.D.4; Odze, Robert D., M.D., F.R.C.P.C.1

American Journal of Gastroenterology: January 2008 - Volume 103 - Issue 1 - p 38–47
ORIGINAL CONTRIBUTIONS: ESOPHAGUS
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OBJECTIVES Photodynamic therapy (PDT) is increasingly used for the treatment of patients with Barrett's esophagus (BE) with dysplasia or early carcinoma. Post-PDT, some patients show residual BE either exposed to the luminal surface (nonburied) or buried underneath reepithelialized squamous mucosa (buried BE). Buried BE may be a serious clinical problem since it can go unnoticed during surveillance endoscopies. The neoplastic potential of buried BE is poorly understood. The aim of this study was to evaluate the biological characteristics of nonburied and buried BE in patients treated with PDT.

METHODS Twelve patients selected from a cohort of 52 BE patients who received PDT for high-grade dysplasia or intramucosal adenocarcinoma were used for this study because they all had both pre- and post-PDT (nonburied), and post-PDT buried, BE biopsies, without dysplasia, available for analysis. The biopsies were immunostained for Ki-67, p53, cyclin D1, bcl-2, TGF-α, EGFR, and AMACR. High fidelity DNA histograms were obtained by image cytometry analysis of Feulgen stained slides, and used to determine peak DNA index (DI), DNA heterogeneity, and 5N exceeding rate (5NER). Comparisons were made between pre-PDT nonburied BE and post-PDT nonburied and buried BE.

RESULTS Pre-PDT BE showed an elevated Ki-67 crypt proliferation rate (43.3%) and p53, bcl-2, TGF-α, and EGFR positivity in 8%, 25%, 75%, and 25% of cases, respectively. Cyclin D1 and AMACR were negative in all cases. High fidelity DNA histograms showed mild aneuploidy in 73% of cases. Post-PDT buried BE showed a significantly lower Ki-67 crypt proliferation rate (29.9%) in comparison to nonburied BE, in both pre- PDT (43.3%) and post-PDT (44.4%) biopsies (P < 0.05), but similar rates of positivity for the other peptide markers. In contrast to pre-PDT nonburied BE biopsies, high fidelity DNA histograms revealed that none of the buried BE (0%), and only 2/9 (11%) nonburied BE post-PDT, showed aneuploidy.

CONCLUSIONS Pre-PDT nonburied BE, without dysplasia, shows elevated crypt proliferation and mild, but frequent, DNA content abnormalities. Post-PDT, nonburied BE shows persistently elevated crypt proliferation, but significantly less frequent DNA content abnormalities, whereas buried BE shows decreased crypt proliferation and normal DNA content profile. These results suggest that post-PDT buried BE may have a lower neoplastic potential than pre-PDT BE.

1Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts; 2Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; 3Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and 4Department of Medicine, Boston Healthcare System, Boston, Massachusetts

Presented in part at the 96th annual meeting of the United States and Canadian Academy of Pathology in San Diego, CA, March 24–30, 2007.

Reprint requests and correspondence: Jason L. Hornick, M.D., Ph.D., Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.

Received May 24, 2007; accepted August 15, 2007.

CONFLICT OF INTERESTGuarantor of the article: Jason L. Hornick, M.D., Ph.D.

Specific author contributions: Jason L. Hornick, Raj Goyal, and Robert D. Odze contributed to conception and design of the study. Jason L. Hornick, Mari Mino-Kenudson, Gregory Y. Lauwers, and Weitian Liu collected data or did experiments for the study. Jason L. Hornick, Mari Mino-Kenudson, Weitian Liu, Raj Goyal, and Robert D. Odze contributed to analysis and interpretation of the data. Jason L. Hornick, Mari Mino-Kenudson, Gregory Y. Lauwers, Weitian Liu, Raj Goyal, and Robert D. Odze contributed to drafting the article or revising it critically.

Financial support: DNA ploidy studies were supported in part by NIH grant DK62867 and the Merit Review Award from the research service, Veterans Health Administration.

Potential competing interests: None.

© The American College of Gastroenterology 2008. All Rights Reserved.
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