Barrett's esophagus: cell cycle abnormalities in advancing stages of neoplastic progression

Abstract

Background: Abnormal proliferation in Barrett's esophagus may predispose to the development of esophageal adenocarcinoma, but previous studies have not determined the specific cell cycle abnormalities that were associated with neoplastic progression.

Methods: Ki67/DNA content multiparameter flow cytometry and DNA content flow cytometry were used to investigate G0, G1, and S phase fractions in advancing stages of neoplastic progression in Barrett's esophagus.

Results: In control biopsy specimens from gastric mucosa, G1, S phase, and total Ki67-positive proliferative fractions were low, suggesting that cells were predominantly in G0. Ki67-positive G1 fractions were increased in Barrett's metaplasia. More advanced stages of neoplastic progression were characterized by a subset of biopsy specimens that had aneuploid cell populations, increased S phase fractions, or both.

Conclusions: The development of increased G1 fractions is an early event in Barrett's metaplasia. Increased S phase fractions occur in a subset of specimens typically at more advanced stages of neoplastic progression and often in association with the development of aneuploidy. Neoplastic progression in Barrett's esophagus is associated with at least three types of cell cycle abnormalities: (1) mobilization from G0 into G1; (2) loss of control of the G1/S phase transition; and (3) accumulation in G2.