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CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer.
Mod Pathol. 2007 Dec; 20(12):1286-97.MP

Abstract

Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer.

Authors+Show Affiliations

Oncology Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17906616

Citation

Liu, Qiang, et al. "CDX2 Expression Is Progressively Decreased in Human Gastric Intestinal Metaplasia, Dysplasia and Cancer." Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, vol. 20, no. 12, 2007, pp. 1286-97.
Liu Q, Teh M, Ito K, et al. CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer. Mod Pathol. 2007;20(12):1286-97.
Liu, Q., Teh, M., Ito, K., Shah, N., Ito, Y., & Yeoh, K. G. (2007). CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 20(12), 1286-97.
Liu Q, et al. CDX2 Expression Is Progressively Decreased in Human Gastric Intestinal Metaplasia, Dysplasia and Cancer. Mod Pathol. 2007;20(12):1286-97. PubMed PMID: 17906616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer. AU - Liu,Qiang, AU - Teh,Ming, AU - Ito,Kosei, AU - Shah,Nilesh, AU - Ito,Yoshiaki, AU - Yeoh,Khay Guan, Y1 - 2007/09/28/ PY - 2007/10/2/pubmed PY - 2008/2/21/medline PY - 2007/10/2/entrez SP - 1286 EP - 97 JF - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JO - Mod. Pathol. VL - 20 IS - 12 N2 - Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer. SN - 0893-3952 UR - https://www.unboundmedicine.com/medline/citation/17906616/CDX2_expression_is_progressively_decreased_in_human_gastric_intestinal_metaplasia_dysplasia_and_cancer_ L2 - http://dx.doi.org/10.1038/modpathol.3800968 DB - PRIME DP - Unbound Medicine ER -