Expression of CDX2 and LI-cadherin in intestinal metaplasia and adenocarcinoma of the stomach

Abstract

Background and aims: CDX2 and Li-cadherin are intestinal specific markers that are normally only found in small intestine and colon. CDX2 is a caudal-related homeobox transcription factor that regulates intestinal development, differentiation and maintenance of the intestinal phenotype. It regulates Li-cadherin in colorectal cell line model, HT29. Since a step-wise progression from normal mucosa through gastritis, intestinal metaplasia and dysplasia to adenocarcinoma has been suggested for gastric cancer, we hypothesized that the intestinal markers CDX2 and Li-cadherin might be expressed in gastric cancer. The aim of this study is to investigate the expression of CDX2 and Li-cadherin in gastric cancer. Methods: 80 pairs of tumor and adjacent non-cancerous gastric mucosa were collected from gastrectomy specimens. Semi-quantitative RT-PCR was utilized to study the mRNA expression levels of CDX2 and Li-cadherin. Protein expression levels of CDX2 and Li-cadherin were determined by immunohistochemical staining. Results: The mRNA of CDX2 (56%) and Li-cadherin (70%) were over-expressed in tumor as compared to adjacent non-cancerous mucosa. Over-expression of Li-cadherin was significantly associated with CDX2. Over-expression of CDX2 and Li-cadherin were found to be associated with lymph node metastasis (p < 0.05). Immunohistochemical staining indicated that the expression of CDX2 and Li-cadherin were strongly co-localized in intestinal metaplasia and adenocarcinoma but absent in normal gastric mucosa. Conclusions: Over-expression of CDX2 and Li-cadherin was found in gastric adenocarcinoma. Expression of CDX2 and Li-cadherin were associated with lymph node metastasis. The co-localization of CDX2 and Li-cadherin during intestinal metaplasia may suggest a role in gastric carcinogenesis.