Expressions of CDX-2 and LI-cadherin in Gastric Benign Lesions and Tumor and Its Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Shiqi ¹ , NIU Jianhua ² , LvYi ¹ , MU Lati ² , WANG Yixun ³ , XIN Guohong. ⁴

1.Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China;;
2.Department of Gastrointestinal Surgery, The First Affiliated Hospital of Medicine School, Shihezi University, Shihezi 832002, Xinjiang Uygur Autonomous Region, China;;

Corresponding author：

Keywords：

Gastric neoplasm; Gastric benign lesion; Immunohistochemistry; Caudal type homeobox transcription factor-2; Liver-intestine cadherin

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ObjectiveTo investigate the potential role of caudal type homeobox transcription factor-2 (CDX-2) and liverintestine cadherin (LI-cadherin) in the development and progression of gastric tumor by detecting their expressions in gastric cancer and benign lesions. MethodsThe expressions of CDX-2 and LI-cadherin protein were detected by immunohistochemistry in normal gastric mucosa (n=28), chronic superficial gastritis (n=30), chronic atrophic gastritis (n=42), intestinal metaplasia (n=58), gastric adenocarcinoma (n=46), vicinity cancerous tissue (n=30), and gastric stromal tumor (n=10)．Then, the relationship between expression of CDX-2 or LI-cadherin protein and clinicopathologic features was analyzed． Results①The expressions of CDX-2 and LI-cadherin were all negative in normal gastric mucosa, chronic superficial gastritis, vicinity cancerous tissue, and gastric stromal tumor. The positive rates of CDX-2 protein expression in intestinal metaplasia and gastric adenocarcinoma were 91.4% (53/58) and 80.4% (37/46), respectively, and the positive rates of LI-cadherin protein expression were 82.8% (48/58) in intestinal metaplasia and 65.2% (30/46) in gastric adenocarcinoma. The positive rates of CDX-2 and LI-cadherin protein expression in intestinal type gastric adenocarcinoma 〔90.6% (29/32) and 78.1% (25/32)〕 were higher than those in diffuse type gastric adenocarcinoma 〔57.1% (8/14) and 35.7% (5/14)〕, P lt;0.05． ② CDX-2 protein expression was associated with degree of differentiation (P=0.007), and LI-cadherin protein expression was associated with lymph node metastasis (P=0.007) and cancer staging (P=0.013). ③ In the mucosa of intestinal metaplasia, the coexpression positive rate of CDX-2 protein expression in nucleus with LI-cadherin protein in cytoplasm or membrane was 83.0% (44/53), while the coexpression positive rate was 67.6% (25/37) in gastric adenocarcinoma. Although b tendency between CDX-2 and LI-cadherin protein expression was showed, it was not confirmed by the correlation analysis (r=238， P=0.115). ConclusionsThe abnormal expressions of CDX-2 and LI-cadherin may be involved in the development and progress of intestinal metaplasia and gastric adenocarcinoma, respectively, and further studies are needed to determine if they have synergistic effect.

Citation： LIU Shiqi,NIU Jianhua,LvYi,MU Lati,WANG Yixun,XIN Guohong.. Expressions of CDX-2 and LI-cadherin in Gastric Benign Lesions and Tumor and Its Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(9): 936-941. doi: Copy

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2.	Deb K, Sivaguru M, Yong HY, et al. CDX2 gene expression and trophectoderm lineage specification in mouse embryos [J]. Science, 2006, 311(5763): 992996.
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7.	吴肇汉, 吴在德. 外科学 [M].第8版. 北京: 人民卫生出版社, 2008: 438.
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13.	Sung MT, Zhang S, Maclennan GT, et al. Histogenesis of clear cell adenocarcinoma in the urinary tract: evidence of urothelial origin [J]. Clin Cancer Res, 2008, 14(7): 19471955.
14.	Dong WG, Yu QF, Xu Y, et al. Licadherin is inversely correlated with galectin3 expression in gastric cancer [J]. Dig Dis Sci, 2008, 53(7): 18111817.
15.	郑见宝，孙学军，王炜，等． HIF1α与CDX2在结直肠腺癌组织中的表达及意义 [J]．中国普外基础与临床杂志， 2010， 17(12)： 12651269．.
16.	Hinoi T, Lucas PC, Kuick R, et al. CDX2 regulates liver intestinecadherin expression in normal and malignant colon epithelium and intestinal metaplasia [J]. Gastroenterology, 2002, 123(5): 15651577.
17.	Mutoh H, Hayakawa H, Sakamoto H, et al. Homeobox protein CDX2 reduces COX2 transcription by inactivating the DNAbinding capacity of nuclear factorkappaB [J]. J Gastroenterol, 2007, 42(9): 719729.
18.	Pacheco II, Macleod RJ. CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucraseisomaltase using Ror2 on intestinal epithelia [J]. Am J Physiol Gastrointest Liver Physiol, 2008, 295(4): G748G759.
19.	Wani Y, Notohara K, Nakatani Y, et al. Aberrant nuclear CDX2 expression in moruleforming tumours in different organs, accompanied by cytoplasmic reactivity [J]. Histopathology, 2009, 55(4): 465468.
20.	Sung MT, Lopezbeltran A, Eble JN, et al. Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder [J]. Mod Pathol, 2006, 19(11): 13951401.
21.	Sung MT, Zhang S, Lopezbeltran A, et al. Urothelial carcinoma following augmentation cystoplasty: an aggressive variant with distinct clinicopathological characteristics and molecular genetic alterations [J]. Histopathology, 2009, 55(2): 161173.
22.	Houghton O, Connolly LE, Mccluggage WG. Morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor CDX2 [J]. Histopathology, 2008, 53(2): 156165.

1. Tahara E. Genetic pathways of two types of gastric cancer [J]. IARC Sci Publ, 2004(157): 327349.
2. Deb K, Sivaguru M, Yong HY, et al. CDX2 gene expression and trophectoderm lineage specification in mouse embryos [J]. Science, 2006, 311(5763): 992996.
3. Manzo BA, Crabtree JE, Fiona CM, et al. Helicobacter pylori regulates the expression of inhibitors of DNA binding (Id) proteins by gastric epithelial cells [J]. Microbes Infect, 2006, 8(4): 10641074.
4. Wendeler MW, Jung R, Himmelbauer H, et al. Unique gene structure and paralogy define the 7Dcadherin family [J]. Cell Mol Life Sci, 2006, 63(13): 15641573.
5. Berndorff D, Gessner R, Kreft B, et al. Liverintestine cadherin: molecular cloning and characterization of a novel Ca2+dependent cell adhesion molecule expressed in liver and intestine [J]. J Cell Biol, 1994, 125(6): 13531369.
6. Ko S, Chu KM, Luk JM, et al. Overexpression of LIcadherin in gastric cancer is associated with lymph node metastasis [J]. Biochem Biophys Res Commun, 2004, 319(2): 562568.
7. 吴肇汉, 吴在德. 外科学 [M].第8版. 北京: 人民卫生出版社, 2008: 438.
8. Sobin LH, Fleming ID. TNM Classification of Malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer [J]. Cancer, 1997, 80(9): 18031804.
9. Mutoh H, Sakurai S, Satoh K, et al. Development of gastric carcinoma from intestinal metaplasia in CDX2transgenic mice [J]. Cancer Res, 2004, 64(21): 77407747.
10. Gao N, White P, Kaestner KH. Establishment of intestinal identity and epithelialmesenchymal signaling by CDX2 [J]. Dev Cell, 2009, 16(4): 588599.
11. Shiotani A, Kamada T, Yamanaka Y, et al. Sonic hedgehog and CDX2 expression in the stomach [J]. J Gastroenterol Hepatol, 2008, 23(Suppl 2): S161S166.
12. Kim HS, Lee JS, Freund JN, et al. CDX2 homeobox gene expression in human gastric carcinoma and precursor lesions [J]. J Gastroenterol Hepatol, 2006, 21(2): 438442.
13. Sung MT, Zhang S, Maclennan GT, et al. Histogenesis of clear cell adenocarcinoma in the urinary tract: evidence of urothelial origin [J]. Clin Cancer Res, 2008, 14(7): 19471955.
14. Dong WG, Yu QF, Xu Y, et al. Licadherin is inversely correlated with galectin3 expression in gastric cancer [J]. Dig Dis Sci, 2008, 53(7): 18111817.
15. 郑见宝，孙学军，王炜，等． HIF1α与CDX2在结直肠腺癌组织中的表达及意义 [J]．中国普外基础与临床杂志， 2010， 17(12)： 12651269．.
16. Hinoi T, Lucas PC, Kuick R, et al. CDX2 regulates liver intestinecadherin expression in normal and malignant colon epithelium and intestinal metaplasia [J]. Gastroenterology, 2002, 123(5): 15651577.
17. Mutoh H, Hayakawa H, Sakamoto H, et al. Homeobox protein CDX2 reduces COX2 transcription by inactivating the DNAbinding capacity of nuclear factorkappaB [J]. J Gastroenterol, 2007, 42(9): 719729.
18. Pacheco II, Macleod RJ. CaSR stimulates secretion of Wnt5a from colonic myofibroblasts to stimulate CDX2 and sucraseisomaltase using Ror2 on intestinal epithelia [J]. Am J Physiol Gastrointest Liver Physiol, 2008, 295(4): G748G759.
19. Wani Y, Notohara K, Nakatani Y, et al. Aberrant nuclear CDX2 expression in moruleforming tumours in different organs, accompanied by cytoplasmic reactivity [J]. Histopathology, 2009, 55(4): 465468.
20. Sung MT, Lopezbeltran A, Eble JN, et al. Divergent pathway of intestinal metaplasia and cystitis glandularis of the urinary bladder [J]. Mod Pathol, 2006, 19(11): 13951401.
21. Sung MT, Zhang S, Lopezbeltran A, et al. Urothelial carcinoma following augmentation cystoplasty: an aggressive variant with distinct clinicopathological characteristics and molecular genetic alterations [J]. Histopathology, 2009, 55(2): 161173.
22. Houghton O, Connolly LE, Mccluggage WG. Morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor CDX2 [J]. Histopathology, 2008, 53(2): 156165.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of CDX-2 and LI-cadherin in Gastric Benign Lesions and Tumor and Its Significance

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