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http://dx.doi.org/10.7314/APJCP.2012.13.1.247

Expression of CDX2 and Villin in Gastric Cardiac Intestinal Metaplasia and the Relation with Gastric Cardiac Carcinogenesis  

Xiao, Zhong-Yue (Department of Oncology, Cancer Institute, the First Affiliated Hospital of Henan University of Science and Technology)
Ru, Yi (Department of Oncology, Cancer Institute, the First Affiliated Hospital of Henan University of Science and Technology)
Sun, Jiang-Tao (Department of Oncology, Cancer Institute, the First Affiliated Hospital of Henan University of Science and Technology)
Gao, She-Gan (Department of Oncology, Cancer Institute, the First Affiliated Hospital of Henan University of Science and Technology)
Wang, Yu-Feng (Department of Oncology, Cancer Institute, the First Affiliated Hospital of Henan University of Science and Technology)
Wang, Li-Dong (Henan Key Laboratory for Esophageal Cancer Research, College of Medicine, Zhengzhou University)
Feng, Xiao-Shan (Department of Oncology, Cancer Institute, the First Affiliated Hospital of Henan University of Science and Technology)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.1, 2012 , pp. 247-250 More about this Journal
Abstract
Objective: To determine whether CDX2 and villin protein expression are associated with intestinal metaplasia (IM) in gastric cardiac mucosa and to explore the relationship with evolution of gastric cardiac adenocarcinoma (GCA). Methods: We studied 143 gastric cardiac biopsy or resection specimens from Henan province China, including 25 cardiac gastritis specimens with IM, 65 dysplasia specimens with IM and 35 gastric cardiac adenocarcinoma specimens and stained them for CDX2 and villin by the immunohistochemical SP method. 15 normal gastric cardiac biopsy specimens were also collected as control. Results: (1) Normal gastric mucosa presented no CDX2 and villin expression. The positive rates of CDX2 protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 84.0% (21/25), 66.7% (32/48) and 36.4% (20/55), respectively. While the positive rates of villin protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 76.0% (19/25), 70.8% (34/48) and 45.5% (25/55), respectively. There were significant differences among the three groups for both CDX2 and villin (P<0.01). Spearman's rank correlation coefficient(rho) showed a close correlation between the two proteins (r=0.843, P<0.01) and both were positively related with tumor differentiation (both P<0.05), but not associated with age, sex, invasion and metastasis of lymph node (P>0.05). Conclusion: Our results suggest that ectopic expression of CDX2 and villin may be involved in early-stage IM and tumorigenesis in gastric cardia and the expression of villin may be regulated by CDX2.
Keywords
CDX2; villin; gastric cardiac; intestinal metaplasia; adenocarcinoma; protein expression;
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1 Regalado SP, Nambu Y, Iannettoni MD, et al (1998). Abundant expression of the intestinal protein villin in Barrett's metaplasia and esophageal adenocarcinomas. Mol Carcinog, 22, 182-9.   DOI
2 Shi XY, Bhagwandeen B, Leong AS (2008). CDX2 and villin are useful markers of intestinal metaplasia in the diagnosis of Barrett esophagus. Am J Clin Pathol, 129, 571-7.   DOI
3 Siewert JR, Stein HJ, Feith M (2006). Adenocarcinoma of the esophago-gastric junction. Scand J Surg, 95, 260-9.   DOI
4 Silberg DG, Sullivan J, Kang E, et al (2002). Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice. Gastroenterology, 122, 689-96.   DOI
5 Silberg DG, Swain GP, Suh ER, et al (2000). Cdx1 and cdx2 expression during intestinal development. Gastroenterology, 119, 961-71.   DOI
6 Tsukamoto T, Inada K, Tanaka H, et al (2004). Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia. J Cancer Res Clin Oncol, 130, 135-45.   DOI
7 Villanacci V, Rossi E, Zambelli C, et al (2007). COX-2, CDX2, and CDC2 immunohistochemical assessment for dysplasiacarcinoma progression in Barrett's esophagus. Dig Liver Dis, 39, 305-11.   DOI
8 Weimann A, Rieger A, Zimmermann M, et al (2010). Comparison of six immunohistochemical markers for the histologic diagnosis of neoplasia in Barrett's esophagus. Virchows Arch, 457, 537-45.   DOI
9 Yamamichi N, Inada K, Furukawa C, et al (2009). Cdx2 and the Brm-type SWI/SNF complex cooperatively regulate villin expression in gastrointestinal cells. Exp Cell Res, 315, 1779-89.   DOI
10 Zhao CB, Zhou CJ, Guo JQ (2009). Expression of villin in precancerous lesions and gastric carcinoma and its clinical significance. J ShanDong University Med Sci, 47, 46-9
11 Eda A, Osawa H, Yanaka I, et al (2002). Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia. J Gastroenterol, 37, 94-100.   DOI
12 Fitzgerald RC, Omary MB, Triadafilopoulos G (1997). Acid modulation of HT29 cell growth and differentiation. An in vitro model for Barrett's esophagus. J Cell Sci, 110, 663-71.
13 Gao SG, Wang LD, Fan ZM, et al (2005). Histochemical studies on intestinal metaplasia adjacent to gastric cardia adenocarcinoma in subjects at high-incidence area in Henan, north China. World J Gastroenterol, 11, 4634-7.   DOI
14 Guo RJ, Suh ER, Lynch JP (2004). The role of Cdx proteins in intestinal development and cancer. Cancer Biol Ther, 3, 593-601.   DOI
15 Kerkhof M, Bax DA, Moons LM, et al (2006). Does CDX2 expression predict Barrett's metaplasia in oesophageal columnar epithelium without goblet cells? Aliment Pharmacol Ther, 24, 1613-21.   DOI
16 McColl KE (2006). Cancer of the gastric cardia. Best Pract Res Clin Gastroenterol, 20, 687-96.   DOI
17 Mesquita P, Jonckheere N, Almeida R, et al (2003). Human MUC2 mucin gene is transcriptionally regulated by Cdx homeodomain proteins in gastrointestinal carcinoma cell lines. J Biol Chem, 278, 51549-56.   DOI
18 Mutoh H, Sakurai S, Satoh K, et al (2004). Development of gastric carcinoma from intestinal metaplasia in Cdx2- transgenic mice. Cancer Res, 64, 7740-7.   DOI
19 Odze RD (2005). Unraveling the mystery of the gastroesophageal junction: a pathologist's perspective. Am J Gastroenterol, 100, 1853-67.   DOI
20 Niwa T, Ikehara Y, Nakanishi H, et al (2005). Mixed gastricand intestinal-type metaplasia is formed by cells with dual intestinal and gastric differentiation. J Histochem Cytochem, 53, 75-85.   DOI
21 Palli D, Bianchi S, Decarli A, et al (1992). A case-control study of cancers of the gastric cardia in Italy. Br J Cancer, 65, 263-6.   DOI
22 Athman R, Louvard D, Robine S (2002). The epithelial cell cytoskeleton and intracellular trafficking. III. How is villin involved in the actin cytoskeleton dynamics in intestinal cells? Am J Physiol Gastrointest Liver Physiol, 283, G496- 502.   DOI
23 Eda A, Osawa H, Satoh K, et al (2003). Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa. J Gastroenterol, 38, 14-22.   DOI
24 Blot WJ, Devesa SS, Kneller RW, et al (1991). Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA, 265, 1287-9.   DOI
25 Botterweck AA, Schouten LJ, Volovics A, et al (2000). Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol, 29, 645-54.   DOI
26 Dudouet B, Robine S, Huet C, et al (1987). Changes in villin synthesis and subcellular distribution during intestinal differentiation of HT29-18 clones. J Cell Biol, 105, 359-69.   DOI