CDX-2 homeobox gene expression in human gastric carcinoma and precursor lesions

Abstract

Background: Recent studies have demonstrated that CDX-2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer. To address the role of CDX-2 in carcinogenesis of gastric carcinomas of intestinal type, the expression of CDX-2 in gastric carcinoma and precursor lesions were examined using immunohistochemistry.

Methods: A total of 160 specimens diagnosed as gastric carcinomas or non-invasive neoplasia from 158 patients were analyzed for CDX-2 expression by immunochemical methods. Patients were classified into histopathologic subgroups according to the Padova international classification: 60 cases of low-grade non-invasive neoplasia, 55 cases of high grade, and 45 cases of invasive intestinal-type adenocarcinoma. The CDX-2 expression in non-neoplastic gastric mucosa including intestinal metaplasia was also evaluated in the areas included in the histologic sections.

Results: The CDX-2 expression was localized in the epithelial cell nuclei in the area of intestinal metaplasia with or without dysplasia and carcinoma, consistent with its role as a transcriptional regulator. No CDX-2 reactivity was noted in the normal mucosa in all cases. The CDX-2 expression was detected in 73.3% of low-grade cases, 85.5% of high-grade cases and 91.1% of intestinal-type adenocarcinoma cases. In the gastric mucosa with intestinal metaplasia, 89.7% of the samples were positive. The CDX-2-expressing cells in intestinal metaplasia were more prevalent than in dysplasia and carcinoma. Expression of CDX-2 showed a statistically significant positive correlation with increasing grade of dysplasia and carcinoma.

Conclusions: These findings suggest that CDX-2 expression in stomach cancer may be a marker of the progression of gastric carcinogenesis, and that its activation may represent an early event.