CDX2 hox gene product in a rat model of esophageal cancer.
BACKGROUND
Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis.


METHODS
The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: <10 weeks; Group B: 10-30 weeks; Group C: >30 weeks).


RESULTS
No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001).


CONCLUSIONS
De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma.
Ingravallo
Giuseppe
G
Department of Medical Diagnostic Sciences & Special Therapies, Pathology Unit, University of Padova, Padova, Italy. pepino@uniba.it
Dall'Olmo
Luigi
L
Segat
Daniela
D
Fassan
Matteo
M
Mescoli
Claudia
C
Dazzo
Emanuela
E
Castoro
Carlo
C
Polimeno
Lorenzo
L
Rizzetto
Christian
C
Baroni
Maurizio David
MD
Zaninotto
Giovanni
G
Ancona
Ermanno
E
Rugge
Massimo
M
D000818:Animals; D001471:Barrett Esophagus / Q000473:pathology; D000071616:CDX2 Transcription Factor; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D000071616:CDX2 Transcription Factor; C541055:Cdx2 protein, rat; D018398:Homeodomain Proteins; D014157:Transcription Factors