Abnormal expression of biomarkers in incompletely ablated Barrett's esophagus.
OBJECTIVE
The aim of this study was to evaluate expression of cancer risk-associated biomarkers in columnar epithelium at squamocolumnar junctions produced by an ablation procedure and proton pump inhibitors in incompletely ablated Barrett's esophagus (BE) patients that were nondysplastic prior to ablation.


BACKGROUND
Ablation of BE to squamous epithelium is achievable by combining a re-injury method with acid suppression. We previously reported that, when there is complete ablation, the neo-squamous epithelium is normal histologically and in biomarker expression. However, squamous islands observed after prolonged use of PPIs were associated with abnormalities in p53 expression and Ki-67 labeling.


METHODS
Twenty-one nondysplastic BE cases with incomplete ablation were evaluated for the expression of Ki-67 (proliferation), cyclooxygenase-2 (COX-2), and p53 by immunohistochemistry.


RESULTS
Pre-ablation biopsies showed the normal staining patterns in columnar epithelium, ie, normal Ki-67 labeling, rare positive COX-2 staining of interstitial cells, and negative or mild staining for p53 in the majority of patients' biopsies. However, post-ablation biopsies demonstrated abnormal staining patterns in the glandular area at the new squamocolumnar junctions. In 13 of 21 post-ablation cases (62%), increased Ki-67 staining was seen in BE glands. In 8 of 21 patients (38%), increased COX-2 expression was seen in columnar epithelium. Similarly, in 8 of 21 post-ablation junctions (38%), there was increased p53 staining.


CONCLUSIONS
Our findings of increased expression of cancer-associated biomarkers in incompletely ablated BE patients raise a cautionary note regarding this procedure. We hypothesize that newly formed junctions contain cells undergoing replication, differentiation, etc, and are thus more susceptible to genomic damage.
Dvorak
Katerina
K
Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, AZ, USA.
Ramsey
Lois
L
Payne
Claire M
CM
Sampliner
Richard
R
Fass
Ronnie
R
Bernstein
Harris
H
Prasad
Anil
A
Garewal
Harinder
H
D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004564:Electrocoagulation; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019394:Ki-67 Antigen; D054328:Proton Pump Inhibitors; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2