Gene expression profiling reveals stromal genes expressed in common between Barrett's esophagus and adenocarcinoma.

BACKGROUND & AIMS: Barrett's esophagus is a precursor of esophageal adenocarcinoma. DNA microarrays that enable a genome-wide assessment of gene expression enhance the identification of specific genes as well as gene expression patterns that are expressed by Barrett's esophagus and adenocarcinoma compared with normal tissues. Barrett's esophagus length has also been identified as a risk factor for progression to adenocarcinoma, but whether there are intrinsic biological differences between short-segment and long-segment Barrett's esophagus can be explored with microarrays. METHODS: Gene expression profiles for endoscopically obtained biopsy specimens of Barrett's esophagus or esophageal adenocarcinoma and associated normal esophagus and duodenum were identified for 17 patients using DNA microarrays. Unsupervised and supervised approaches for data analysis defined similarities and differences between the tissues as well as correlations with clinical phenotypes. RESULTS: Each tissue displays a unique expression profile that distinguishes it from others. Barrett's esophagus and esophageal adenocarcinoma express a unique set of stromal genes that is distinct from normal tissues but similar to other cancers. Adenocarcinoma also showed lower and higher expression for many genes compared with Barrett's esophagus. No difference in gene expression was found between short-segment and long-segment Barrett's esophagus. CONCLUSIONS: The genome-wide assessment provided by current DNA microarrays reveals many candidate genes and patterns not previously identified. Stromal gene expression in Barrett's esophagus and adenocarcinoma is similar, indicating that these changes precede malignant transformation.

Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta-analysis.

BACKGROUND: Published data on the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis are conflicting. A meta-analysis was performed to synthesize available publications and to compare the risk of colorectal neoplasia in patients with ulcerative colitis with and without primary sclerosing cholangitis. METHODS: By using MEDLINE and manual search methods, studies were identified that compared the risk of colorectal neoplasia (dysplasia and carcinoma) in patients with ulcerative colitis with and without primary sclerosing cholangitis. In addition, citations were reviewed in relevant articles and proceedings from gastroenterology meetings, and investigators were contacted when data were incomplete. The summary odds ratio (OR) was then calculated for the risk for patients with ulcerative colitis and primary sclerosing cholangitis of having colorectal neoplasia develop compared with that of patients with ulcerative colitis without primary sclerosing cholangitis. RESULTS: Eleven studies met all eligibility criteria for the meta-analysis. Patients with ulcerative colitis and primary sclerosing cholangitis are at increased risk of colorectal dysplasia and carcinoma compared with patients with ulcerative colitis alone; OR 4.79: 95% CI [3.58, 6.41] with the Mantel-Haenszel method, and OR 5.11: 95% CI [3.15, 8.29] with the Der Simonian and Laird method. This increased risk is present even when the risk of colorectal carcinoma alone is considered; OR 4.09: 95% CI [2.89, 5.76] and OR 4.26: 95% CI [2.80, 6.48] by using, respectively, the Mantel-Haenszel and the Der Simonian and Laird methods. CONCLUSIONS: Patients with ulcerative colitis and primary sclerosing cholangitis have a significantly higher risk for the development of colorectal neoplasia than patients with ulcerative colitis but not primary sclerosing cholangitis. More intensive colonoscopic surveillance should be considered for patients with ulcerative colitis and primary sclerosing cholangitis.