Correlation between dysplasia and mutations of six tumor suppressor genes in Barrett's esophagus

Background. Barrett's esophagus (BE) may progress to adenocarcinoma through dysplastic progression. Classification of dysplasia in BE has significant interobserver variability. Our objective was to determine whether genetic a lterations in BE correlate with degrees of histo logic dysplasia. Methods. Fixed tissue from 37 patients with BE and adenocarcinoma was studi ed for six tumor suppressor genes. Tissues were microdissected and analyzed for loss of heterozygosity. Microdissection of individual crypts showing m etaplasia and dysplasia were performed and analyzed for 23 of the 37 patien ts whose tumors were heterozygous for at least four of the six genes studie d. Results. Frequency of alterations for MXI1, hOGG1, p53, MTS1, DCC, and APC were 7 of 32 (22%), 12 of 35 (34%), 12 of 26 (46%), 17 of 30 (57%), 17 of 2 7 (63%), and 23 of 36 (64%), respectively. Analysis of BE demonstrated that crypts with metaplasia, low-grade dysplasia, and high-grade dysplasia stro ngly correlated with alterations in tumor suppressor genes (p < 0.0001). Conclusions. This pilot study demonstrates that genetic analysis can be per formed on individual crypts in patients with BE, and that alterations may f acilitate objective classification of the severity of dysplasia. (C) 2001 b y The Society of Thoracic Surgeons.