Variation in proliferative and cell cycle markers in Barrett's esophagus in relation to circumferential and axial location in the esophagus
Umar, Nosheen Alleyne, Lance Cheung, Danny Rees, James Trudgill, Caitlin Zanetto, Ulises Muzaffar, Suhail
Umar, Nosheen
Alleyne, Lance
Cheung, Danny
Rees, James
Trudgill, Caitlin
Zanetto, Ulises
Muzaffar, Suhail
Abstract
Background: Adenocarcinoma in Barrett's esophagus (BE) occurs more frequently between 12 and 3 o'clock at the gastroesophageal junction (GEJ). Methods: BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined. Results: 110 patients: median age 64 (IQR, 56-71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6-5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o'clock, and overall was 49.6% higher in the 12-6 o'clock position compared to 6-12 o'clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00-2.12)]. A similar pattern was found with p21 [1.82 (1.00-3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29-2.34)]; Cyclo-oxygenase 2 [2.03 (1.48-2.78]) and p21 [2.06 (1.16-3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43-0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma. Conclusion: Increased cellular proliferation was seen at 12-6 o'clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE.
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Date
2024-01-22
Type
Article
Subject
Gastroenterology
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Citation
Umar N, Alleyne L, Cheung D, Rees J, Trudgill C, Zanetto U, Muzaffar S, Trudgill N. Variation in proliferative and cell cycle markers in Barrett's esophagus in relation to circumferential and axial location in the esophagus. Eur J Gastroenterol Hepatol. 2024 Mar 1;36(3):306-312. doi: 10.1097/MEG.0000000000002700
Journal / Source Title
European Journal of Gastroenterology and Hepatology
DOI
10.1097/MEG.0000000000002700
PMID
38251437
Publisher
Lippincott, Williams & Wilkins