The gene expression profile of cardia intestinal metaplasia is similar to that of Barrett's esophagus, not gastric intestinal metaplasia.

The etiology and significance of cardia intestinal metaplasia (CIM) is disputed. CIM may represent a form of Barrett's esophagus due to reflux or could reflect generalized gastric intestinal metaplasia due to Helicobacter pylori. The aim of this study was to utilize gene expression data to compare CIM to Barrett's and gastric intestinal metaplasia. Endoscopic biopsies were classified by endoscopic and histologic criteria as CIM (n= 33), Barrett's (n= 25), or gastric intestinal metaplasia of the antrum or body (n= 18). The squamocolumnar and gastroesophageal junctions were aligned in CIM patients and patients with diffuse gastric intestinal metaplasia were excluded. H. pylori was tested for in the biopsies of all patients. After laser-capture microdissection, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression of a panel of nine genes that has been shown to differentiate Barrett's from other foregut mucosa. Cluster analysis with linear discriminant analysis of the expression data was used to classify each sample into groups based solely on similarity of gene expression. Cluster analysis was performed for three groups (CIM vs. Barrett's vs. gastric intestinal metaplasia) and two groups (CIM + Barrett's vs. gastric intestinal metaplasia). There was no difference in H. pylori infection among groups (P= 0.66). Clustering into three groups resulted in frequent misclassification between CIM and Barrett's while misclassification of gastric intestinal metaplasia was uncommon. The CIM and Barrett's groups were then combined for two group clustering and linear discriminant analysis correctly predicted 95% of CIM and Barrett's samples and 83% of gastric intestinal metaplasia samples based on gene expression alone. In conclusion, the gene expression profiles of CIM and Barrett's esophagus were similar in 95% of biopsies and differed significantly from that of gastric intestinal metaplasia. The indistinguishable gene expression profile of CIM and BE suggests that they may share a common etiology in the majority of patients with a similar biology, and calls into question the perception that CIM is an innocuous process.

[1]  W. Courtney.  Reflux disease (GERD) , 2009 .

[2]  A. Galor,et al.  Transient band keratopathy associated with ocular inflammation and systemic hypercalcemia , 2008, Clinical ophthalmology.

[3]  J. Peters,et al.  Antireflux Surgery Normalizes Cyclooxygenase-2 Expression in Squamous Epithelium of the Distal Esophagus , 2006, The American Journal of Gastroenterology.

[4]  R. Odze.  Unraveling the Mystery of the Gastroesophageal Junction: A Pathologist's Perspective , 2005, The American Journal of Gastroenterology.

[5]  M. Bohrer,et al.  Does Cytokeratin7/20 immunoreactivity help to distinguish Barrett's esophagus from gastric intestinal metaplasia? Results of a prospective study of 75 patients. , 2005, Pathology, research and practice.

[6]  H. Welch,et al.  The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. , 2005, Journal of the National Cancer Institute.

[7]  J. Gong,et al.  Gene expression profiling in Barrett's esophagus and cardia intestinal metaplasia: a comparative analysis using cDNA microarray. , 2004, World journal of gastroenterology.

[8]  H. Gabbert,et al.  Distinction between intestinal metaplasia in the cardia and in Barrett's esophagus: the role of histology and immunohistochemistry. , 2004, Human pathology.

[9]  S. Spechler,et al.  Intestinal metaplasia at the gastroesophageal junction. , 2004, Gastroenterology.

[10]  R. Odze,et al.  Mucin Core Peptide Expression Can Help Differentiate Barrett's Esophagus From Intestinal Metaplasia of the Stomach , 2003, The American journal of surgical pathology.

[11]  P. Chandrasoma.  Pathological Basis of Gastroesophageal Reflux Disease , 2003, World Journal of Surgery.

[12]  S. Spechler,et al.  Intestinal Metaplasia at the Gastroesophageal Junction: Barrett’s, Bacteria, and Biomarkers , 2003, American Journal of Gastroenterology.

[13]  J. Peters,et al.  Cytokeratin and DAS-1 immunostaining reveal similarities among cardiac mucosa, CIM, and Barrett's esophagus , 2002, American Journal of Gastroenterology.

[14]  Geoffrey J McLachlan,et al.  Selection bias in gene extraction on the basis of microarray gene-expression data , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  A. Csendes,et al.  Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia , 2002, American Journal of Gastroenterology.

[16]  J. Goldblum.  The significance and etiology of intestinal metaplasia of the esophagogastric junction. , 2002, Annals of diagnostic pathology.

[17]  J. Goldblum,et al.  Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa , 2002, American Journal of Gastroenterology.

[18]  A. Couvelard,et al.  Cytokeratin immunoreactivity of intestinal metaplasia at normal oesophagogastric junction indicates its aetiology , 2001, Gut.

[19]  D. Graham,et al.  Cytokeratin subsets for distinguishing barrett's esophagus from intestinal metaplasia in the cardia using endoscopic biopsy specimens , 2001, American Journal of Gastroenterology.

[20]  P. Chandrasoma,et al.  Histology of the gastroesophageal junction: an autopsy study. , 2000, The American journal of surgical pathology.

[21]  M. Mayo,et al.  Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia , 2000, Gut.

[22]  J. Goldblum,et al.  Cytokeratin subsets can reliably distinguish Barrett's esophagus from intestinal metaplasia of the stomach. , 1999, Human Pathology.

[23]  A. Sonnenberg,et al.  Characteristics of intestinal metaplasia in the gastric cardia , 1999, American Journal of Gastroenterology.

[24]  R. Wong,et al.  Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and esophagogastric junction: prevalence and clinical data. , 1999, Gastroenterology.

[25]  S. Spechler,et al.  Frequency of intestinal metaplasia at different sites in the esophagus and stomach , 1998 .

[26]  J. Goldblum,et al.  Inflammation and intestinal metaplasia of the gastric cardia: the role of gastroesophageal reflux and H. pylori infection. , 1998, Gastroenterology.

[27]  Robert F. Bonner,et al.  Laser Capture Microdissection: Molecular Analysis of Tissue , 1997, Science.

[28]  A. Bhattacharyya,et al.  Is Barrett's esophagus associated with intestinal metaplasia of the gastric cardia? , 1997, The American journal of gastroenterology.

[29]  J. Peters,et al.  Inflammation and specialized intestinal metaplasia of cardiac mucosa is a manifestation of gastroesophageal reflux disease. , 1997, Annals of surgery.

[30]  J. Peters,et al.  Short-segment Barrett’s esophagus: A prevalent complication of gastroensophageal reflux disease with malignant potential , 1997, Journal of Gastrointestinal Surgery.

[31]  J. Hayward.  The Lower End of the Oesophagus , 1961 .

[32]  J. Peters,et al.  Etiology of intestinal metaplasia at the gastroesophageal junction , 2002, Surgical Endoscopy And Other Interventional Techniques.

[33]  Michael R. Green,et al.  Gene Expression , 1993, Progress in Gene Expression.

[34]  J. Hayward.  The lower end of the oesophagus. , 1961, Thorax.