FLOW CYTOMETRY IN BARRETT'S ESOPHAGUS: WHEN ALL IS SAID AND DONE, MORE IS SAID THAN DONE!

The Seattle group has pioneered the study and application of flow cytometry in Barrett's esophagus in an effort to improve the detection of patients at increased risk of harboring or developing adenocarcinoma (1). In this study, they sought to determine whether aneuploidy (abnormal DNA content within cells) or increased G2/tetraploid fraction (evidence of increased proliferative activity within cells), as determined by flow cytometry, predisposes to neoplastic progression in Barrett's esophagus. Of 210 patients with specialized columnar epithelium studied at the University of Washington, 62 patients without cancer and with adequate follow‐up (mean 34 months) constituted the cohort analyzed in this study. Following their previously well described research biopsy protocol (four quadrant biopsies every 2 cm), one specimen at each level was split for flow cytometry and histologic analysis. Flow cytometry was analyzed by a program devised by one of the authors, and histology was determined by another author. At initial biopsy, 39 patients demonstrated metaplasia only, and 23 had indefinite, low‐grade, or high‐grade dysplasia. Thirteen patients had aneuploidy and/or increased G2/tetraploid fraction, and 20 demonstrated Sphase fractions > 7.0%. In the group of 13 with aneuploidy or increased G2/tetraploid fraction, nine later developed high‐grade dysplasia (4) or adenocarcinoma (5). However, in the group developing cancer, all progressed through a stage of high‐grade dysplasia documented endoscopically prior to the development of adenocarcinoma, and four of five had either high‐grade dysplasia (2) or low‐grade dysplasia (2) at initial endoscopy Three of four developing high‐grade dysplasia initially had low‐grade dysplasia on biopsy. In no patient did high‐grade dysplasia or adenocarcinoma develop without a preceding biopsy showing low‐grade or high‐grade dysplasia. Therefore, using dysplasia alone as a marker of risk would have detected all of these patients. Four of 13 patients with aneuploidy or increased G2 fraction did not develop high‐grade dysplasia during the evaluation period. It is important that none of the patients (0/49) who had neither aneuploidy nor increased G2/tetraploidy progressed to dysplasia or cancer, but three developed aneuploidy and four showed increased G2/tetraploidy during follow‐up. Two of 39 patients demonstrating specialized columnar metaplasia developed high‐grade dysplasia and adenocarcinoma, and both had aneuploidy or increased G2/tetraploidy on initial biopsy, but two others with aneuploidy remain histologically stable. The authors conclude that aneuploidy and increased G2/tetraploidy are precursors of adenocarcinoma in Barrett's esophagus, and that combining flow‐cytometry evaluation with endoscopic biopsies taken according to their intense protocol can be useful in managing patients with Barrett's esophagus. Patients negative for dysplasia and with normal flow cytometry seem to have little cancer risk over a 34‐month follow‐up period and can be followed at 2‐ to 3‐ yr intervals. Those with aneuploidy or increased G2/tetraploidy with specialized columnar epithelium having indefinite or low‐grade dysplasia are followed up at 6‐12 months, and those with high‐grade dysplasia or multiple aneuploid populations are followed‐up at one month, and if confirmed, consideration at that time is given for esophagectomy. This strategy resulted in discovery of early cancer in all but one patient who refused both surveillance and surgery.