Metaplastic esophageal columnar epithelium without goblet cells shows DNA content abnormalities similar to goblet cell-containing epithelium

Abstract

Objectives: The mucosa of patients with columnar-lined esophagus recognized on endoscopy usually shows epithelium with and without goblet cells. Columnar epithelium with goblet cells ("Barrett's esophagus") is generally believed to represent a premalignant lesion and has been shown to contain DNA abnormalities. However, the biological properties of non-goblet columnar epithelium remain unknown. The purpose of this study was to determine the DNA content properties of non-goblet epithelium in patients with metaplastic columnar epithelium of the esophagus.

Methods: Mucosal biopsies of the esophagus from 68 patients with columnar metaplasia of the esophagus (22 without goblet cells and 46 with goblet cells) and 19 patients with normal gastric mucosa (controls) were histologically evaluated for the density of goblet cells. The latter group was divided into low-density, high-density, and very high-density goblet cell subgroups. Tissue sections of non-goblet epithelium and goblet cell epithelium (where present) were evaluated by image cytometry, and high-fidelity DNA histograms were created to indicate the G0/G1 peak DNA index (DI), DNA content heterogeneity index (HI), and the percentage of cells with DNA exceeding 5N (5N-EC). G0/G1 peaks with DI>1.1 were considered aneuploid.

Results: Normal gastric controls showed a mean peak DI of 1.02+/-0.03 and an HI of 11.6+/-0.7. None of the controls revealed aneuploidy or 5N-EC. Patients with metaplastic columnar epithelium with goblet cells showed a DI of 1.15+/-0.12, HI of 18.2+/-2.1, mild aneuploidy in 54% of the cases, and 5N-EC in 15% of the cases, all of which were significantly higher than in controls. Patients with metaplastic columnar epithelium without goblet cells showed DNA content results statistically similar to those of patients with metaplastic columnar epithelium with goblet cells, and also revealed significantly higher values compared with those of controls. Furthermore, there were no significant differences in any of the key DNA content abnormalities between non-goblet and goblet cell-containing epithelium in patients with metaplastic columnar epithelium with goblet cells, or between these two types of epithelium according to the density of goblet cells.

Conclusions: DNA content abnormalities occur with equal frequency and extent in metaplastic columnar epithelium of the esophagus without goblet cells compared with metaplastic columnar epithelium with goblet cells. These findings suggest that metaplastic non-goblet columnar epithelium of the esophagus may have neoplastic potential.

Figure 1

Cellular DNA content in normal gastric mucosa (NGM), all cases of columnar metaplasia (all CM), those with goblet cells (CM-WG), and those with columnar metaplasia without goblet cells (CM-WOG). The bars represent average values±s.d. (a—d) DNA index (DI) values of peaks of the G0/G1 phase, heterogeneity index (HI), aneuploidy rate, and percentage of cells with DI>5N, respectively (a, b). The peak DI and HI values were significantly elevated in all groups of columnar metaplasia compared with normal gastric mucosa (P<0.05), but these values were not different among the columnar metaplasia groups (^†P>0.05). (c) An aneuploidy rate of 0 in NGM, and approximately 50% in cases with columnar metaplasia. (d) Normal gastric mucosa had no cells with DI>5N. However, almost 15% of histograms in the columnar metaplasia groups had at least one cell with DI>5N.

Figure 2

Representative DNA histograms from three separate patients. (a) Normal gastric mucosa, (b) columnar metaplasia without goblet cells, and (c) columnar metaplasia with goblet cells. Note that the DNA histograms of columnar mucosa with or without goblet cells showed similar abnormalities, including aneuploid G0/G1 peaks, elevated heterogeneity index (HI), increased cells in the S phase and occasional cells with DNA index (DI)>5N.