DNA Abnormalities as Marker of Risk for Progression of Barrett's Esophagus to Adenocarcinoma: Image Cytometric DNA Analysis in Formalin-Fixed Tissues

Abstract

OBJECTIVES: To examine DNA content abnormalities in patients with Barrett's esophagus (BE) who progress to esophageal adenocarcinoma, using image cytometric DNA analysis (ICDA) of formalin-fixed tissues. METHODS: Studies were performed on archived biopsies of BE patients' undergoing endoscopic surveillance before developing adenocarcinoma. A comparison group consisted of BE patients' free of cancer during a follow-up period of over 9 yr. Tissue sections were analyzed for the degree of dysplasia and for DNA content abnormalities, using image cytometry. Additional patients were also analyzed in a cross-sectional study of 56 BE cases with and without dysplasia, including 12 cases of adenocarcinoma. RESULTS: Five patients developed adenocarcinoma during follow-up and earlier biopsies obtained before cancer diagnosis showed specialized intestinal metaplasia (SIM) followed by low-grade dysplasia (LGD) in one, SIM followed by high-grade dysplasia (HGD) in one, LGD in two, and HGD in one case. All five showed some DNA abnormality at baseline or in interval biopsies. In the comparison group, five of seven patients showed normal diploid DNA at baseline and on follow-up biopsies. One patient initially had diploid DNA, but developed aneuploidy 11 yr later. Another case initially had aneuploidy, but was diploid on follow-up. Overall, DNA abnormalities were found in 13% of cases with SIM without dysplasia, 60% with LGD, 73% with HGD, and 100% with adenocarcinoma. CONCLUSIONS: (i) Image cytometric DNA analysis is a useful method to examine DNA abnormalities in formalin-fixed tissues and may be more sensitive in predicting progression to adenocarcinoma than HGD. (ii) Histological dysplasia of any grade and DNA abnormalities, help identify BE patients at high risk for adenocarcinoma.