Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa.
BACKGROUND
There have been no detailed reports directly comparing the expression of CDX1 with that of CDX2 in the inflammatory esophageal mucosa and Barrett's epithelium. The present study was designed to examine the expression of CDX 1/2 in inflammatory esophageal mucosa with or without Barrett's epithelium.


METHODS
The expression of CDX1/2 genes was analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) in 34 human esophageal biopsy specimens, and CDX2 expression was also evaluated immunohistochemically, using anti-human CDX2 monoclonal antibody. The biopsy specimens for RNA extraction were taken endoscopically from esophageal mucosa with mucosal break due to gastroesophageal reflux disease (GERD), Barrett's epithelium, and normal epithelium. The expressions of mucin markers (MUC2) and intestine-specific genes (sucrase-isomal-tase, human defensin-5, alkaline phosphatase) were also comparatively analyzed.


RESULTS
CDX1/2 expression was not found in the normal esophageal mucosa. The prevalence of CDX1/2 mRNA expression was significantly higher in the mucosa with Barrett's epithelium than in the mucosa without Barrett's epithelium. It is noteworthy, however, that the CDX2 mRNA expression was initiated at the stage of esophagitis, when neither CDX1 nor intestine-specific genes had emerged yet. In contrast to CDX2, CDX1 was expressed only in Barrett's epithelium. Immunohistochemical study demonstrated strong and extensive nuclear immunoreactivity for CDX2 in Barrett's epithelium. Furthermore, fine granular cytoplasmic staining was also observed in the cytoplasm in Barrett's epithelium, as well as in inflammatory esophageal mucosa.


CONCLUSIONS
We report here, for the first time, that CDX2 is expressed in patients with Barrett's epithelium and inflammatory esophageal mucosa. These findings imply that the expression of CDX2 may be an early event leading to the development of Barrett's esophagus.
Eda
Akashi
A
Department of Internal Medicine, Jichi Medical School, Yakushiji, Kawachi, Tochigi 329-0438, Japan.
Osawa
Hiroyuki
H
Satoh
Kiichi
K
Yanaka
Ichiro
I
Kihira
Ken
K
Ishino
Yumiko
Y
Mutoh
Hiroyuki
H
Sugano
Kentaro
K
D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D004947:Esophagus / Q000737:chemistry*; D005260:Female; D005764:Gastroesophageal Reflux / Q000378:metabolism; D018398:Homeodomain Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators
C491273:CDX1 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators