Richard E. Sampliner

Ornithine decarboxylase activity in Barrett's esophagus: A potential marker for dysplasia

Ornithine decarboxylase activity is known to be increased in certain premalignant conditions. We determined the activity of this enzyme in mucosal biopsy specimens from 15 patients with Barretts esophagus. Ornithine decarboxylase was greater in Barretts mucosa than in squamous esophageal or gastric mucosa. In Barretts mucosa from 4 patients with dysplasia, the enzyme activity was greater than in 11 patients without dysplasia (1.6 +/- 0.35 vs. 0.19 +/- 0.08 U/mg protein; p less than 0.005). Increased ornithine decarboxylase activity in biopsy specimens of Barretts mucosa may represent a marker for dysplasia.

Flow cytometry in Barrett's esophagus. What have we learned so far?

Barretts esophagus is a disease characterized by metaplastic columnar epithelium replacing the stratified squamous lining of the normal esophagus (1). It is associated with an increased risk of adenocarcinoma of the esophagus, estimated to be 30-40 times greater than in the general population. Nevertheless, the actual incidence of cancer is still only about one case per 175-400 patient years of follow-up (2, 3). Since there is presently no way of identifying subgroups of patients with Barretts esophagus who have increased cancer risk, the current clinical recommendation is to perform at least annual surveillance endoscopies in all patients. The only clinical finding leading to increased frequency of surveillance and more aggressive intervention is documentation of dysplasia within the lesion. However, histologic identification of dysplasia is by no means easy and reproducible, there being considerable interobserver variation in pathologic interpretation (4, 5). Therefore, the search continues for more objective markers that might replace or complement dysplasia in the identification of high risk groups. From a clinical and medical cost-containment standpoint; the converse is equally important, i.e., markers that would identify low-risk patients in whom surveillance could either be discontinued or markedly reduced in frequency. Recently, cellular DNA content analysis by flow cytometry has been applied to Barretts esophagus by several investigators. There are many methodologic differences between the reported studies. Some have used fresh tissue obtained at endoscopic biopsies while others have performed analyses on paraffin-fixed sections from surgical specimens. Patients with coexistent Barretts adenocarcinoma are included in some series and not in others. Other technical differences no doubt exist between inves-

Increase in ornithine decarboxylase activity associated with development of dysplasia in Barrett's esophagus.

SummaryA case of Barretts esophagus of the specialized columnar type is described in which mucosal ornithine decarboxylase levels were measured in endoscopic biopsies at two intervals over which severe dysplasia had developed. The Barretts mucosa extended 5 cm above the gastroesophageal junction, was free of dysplasia, and had no detectable ornithine decarboxylase activity at initial evaluation. On follow-up endoscopy one year later, the Barretts mucosa had become dysplastic with a markedly elevated ornithine decarboxylase activity of 1.56 units/mg protein. The patient underwent an esophagectomy because of persistent severe dysplasia and continues to do well postoperatively. Elevated ornithine decarboxylase activity has been described in other premalignant conditions, especially when dysplasia has been present. Further studies in Barretts esophagus are warranted, since ODC activity might prove to be a useful biochemical marker for dysplasia and increased cancer risk.