Helicobacter pylori-induced atrophic gastritis progressing to gastric cancer exhibits sonic hedgehog loss and aberrant CDX2 expression.
BACKGROUND
The loss of sonic hedgehog is an early change that occurs in the mucosa prior to neoplastic transformation and correlates with the type of intestinal metaplasia. Aberrant expression of CDX has also been shown to correlate with the development of intestinal metaplasia.


OBJECTIVE
To examine CDX2 expression in the non-cancerous mucosa of patients with gastric cancer and compared it to CDX2 expression in controls with intestinal metaplasia.


METHODS
Sixty patients who had undergone endoscopic mucosal resection for early gastric cancer and 60 gender- and age-matched controls were studied. Two specimens each were obtained from the greater and lesser curves of the corpus and from the greater curve of the antrum. Expression of CDX2 and sonic hedgehog were evaluated by immunostaining.


RESULTS
Gastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (OR = 8.3; 95%CI, 3.7-18.9, P < 0.001). CDX2 negatively correlated with sonic hedgehog expression, however, multivariate analysis revealed that CDX2 correlated with the intestinal metaplasia scores. Sonic hedgehog indices were lower and CDX2 staining in the corpus lesser curve was higher in the cancer group than in the controls. Sonic hedgehog indices in the corpus decreased and CDX2 indices in both areas increased in patients in the ascending order of those without intestinal metaplasia, those with complete intestinal metaplasia and those with incomplete intestinal metaplasia (P < 0.001).


CONCLUSIONS
Loss of sonic hedgehog expression and aberrant expression of CDX2 correlates with the type of intestinal metaplasia and may play a role in carcinogenesis.
Shiotani
A
A
Health Administration Center, Wakayama University, Wakayama, Japan. shiotani@center.wakayama-u.ac.jp
Iishi
H
H
Uedo
N
N
Ishihara
R
R
Ishiguro
S
S
Tatsuta
M
M
Nakae
Y
Y
Kumamoto
M
M
Hinoi
T
T
Merchant
J L
JL
D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D000071616:CDX2 Transcription Factor; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005757:Gastritis, Atrophic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005773:Gastroscopy; D053823:Hedgehog Proteins / Q000378:metabolism*; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology / Q000302:isolation & purification*; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D000907:Antibodies, Bacterial; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C509239:SHH protein, human