CDX-2和LI-cadherin在胃癌组织中的表达与意义
|
摘要
目的: CDX-2与LI-cadherin在胃癌与癌前病变中的表达情况以及在发生癌变的胃黏膜上皮中的表达和分布至今仍不清楚,通过研究胃癌组织、癌旁组织、正常组胃黏膜组织、胃肠道间质瘤、慢性胃炎及肠化生胃黏膜组织中CDX-2与LI-cadherin的表达水平和分布情况,以及二者的表达阳性率与不同性别胃癌患者中表达的差异、与不同类型胃癌、细胞的分化程度、淋巴结转移程度、胃癌的浸润深度、胃癌的Laurien分期和临床分期的关系,研究二者在胃癌和癌前病变组织中的关系,探索胃黏膜癌前病变及癌变发生的分子机制。
方法:分别应用即用型鼠单克隆抗体(CDX2-88)和羊多克隆抗体(C-17,sc-6987)利用S-P免疫组化检测246例不同胃组织(包括正常胃黏膜30例、慢性浅表性胃炎30例、慢性萎缩性胃炎42例、肠化生胃黏膜58例、胃腺癌46例、癌旁组织30例、胃间质瘤10例) CDX-2与LI-cadherin蛋白的表达情况。
结果:CDX-2基因蛋白在正常胃黏膜及慢性胃炎中不表达;在肠化生组织中阳性表达率为91.4%(53/58);在胃癌组织中阳性表达率为80.4%(37/46),按Laurien分型,肠型胃癌中CDX-2蛋白阳性表达率高于弥漫型胃癌,并有显著性差异(P<0.050) ;CDX-2与细胞分化程度呈高度正相关(P<0.005),但与性别、年龄、浸润深度、胃癌分期及淋巴结转移无关。CDX-2在癌旁组织及胃间质瘤中无表达。LI-cadherin基因蛋白在正常胃黏膜及慢性胃炎中不表达;在肠化生组织中阳性表达率为83%(48/58);在胃腺癌组织中阳性表达率为65%(30/46),按Laurien分型,肠型胃癌中LI-cadherin蛋白阳性表达率(78%)高于弥漫型胃癌(35%),差异有统计学意义(P<0.050) ;LI-cadherin与淋巴结转移及临床分期明显正相关(P<0.010),在癌旁组织及胃间质瘤中无表达。CDX-2与LI-cadherin的过度表达紧密相关,而且CDX-2与LI-cadherin在肠化生胃黏膜中表现出很强的伴随关系。
结论: CDX-2的异常表达可能与胃癌的早期发生有关,且可能是一种抑癌基因,CDX-2高表达胃癌其侵袭性低,细胞分化程度高,因而检测其表达强度有助于判断胃癌恶性程度及胃癌患者的预后。LI-cadherin的异常表达与肠化生及胃腺癌的发生有关, LI-cadherin高表达者淋巴结转移率高,检测其表达强度有助于判断胃癌恶性程度及胃癌患者的预后。CDX-2和LI-cadherine均是肠特异性标记物,而且二者在正常生理情况下均表达于小肠和结肠黏膜。本项研究表明,在胃黏膜肠化生和胃腺癌中CDX-2调节LI-cadherine的表达水平,后者被前者所诱导,尤其是在癌组织发生的初期,二者可能扮重要促癌作用。癌细胞局部侵犯或发生远处转移常常是导致临床治疗失败的主要原因,因此研究胃癌发病的分子机制和生物学行为对于寻找新的抗转移措施是非常关键的。
Objective: CDX-2 and LI-cadherin in gastric cancer and precancerous lesions of the situation and in case of gastric cancer in epithelial expression and distribution are still unclear, through research the CDX-2 and LI-cadherin expression levels and distribution in gastric cancer, adjacent, normal gastric mucosa, Gastrointestinal stromal tumors, chronic gastritis and gastric intestinal metaplasia, and both the expression of different gender and the positive rate of gastric cancer patients in the expression of differences, and different Types of cancer, cell differentiation, metastasis of the depth of invasion of gastric cancer, gastric cancer Laurien stage and the relationship between the clinical stage, to studies the molecular mechanism of gastric cancer about the two factors in gastric cancer and precancerous lesions in the relationship between the exploration and gastric precancerous lesions.
Methods: In this study we examined the expression of caudal-related homeo box transcription factor 2(CDX-2) with monoclonal antibody(CDX2-88)and LI-cadherin with Goat polyclonal antibody(C-17,sc-6987) using SP immunohistochemical detection of 246 cases of various stomach.Including two hundred and forty six specimens were collected,including normal epithelia(n=30), chronic superficial gastritis (n=30), chronic atrophic gastritis(n=42) , intestinal metaplasia (n=58),gastric adenocarcinoma(n=46), nearing cancer(n=30), gastric stromal tumor(n=10).The expression of CDX-2 was detected in alI the tissues by immunohischemistry.
Results: The expression of CDX-2 in normaI epithelia and chronic gastritis are all negative , the positive rates of CDX-2 expresion in intestinal metaplasia and gastric adenocarcinoma are 91.4% and 80.4%,classification with Laurien, the positive rates of CDX-2 expresion in intestinal type and well-differentiated were higher than those in the diffuse type poorly differentiated (P<0.005).The expression of CDX-2 was independence of sex,age,depth of invasion, staging and lymph node metastasis. The nearing cancer and gastric stromal tumor exhibited negative CDX-2 expression.The expression of LI-cadherin in normaI epithelia and chronic gastritis are all negative , the positive rates of LI-cadherin expresion in intestinal metaplasia and gastric adenocarcinoma are 83 % (48/58) and 65 %(30/46),classification with Laurien, the positive rates of LI-cadherin expresion in intestinal type were higher(78%) than those in the diffuse type (35%) (P<0.050).LI-cadherin is positive correlation with lymph node metastasis and staging. The nearing cancer and gastric stromal tumor exhibited negative LI-cadherin expression. LI-cadherin expression closely related to the excessive of CDX-2 in gastric adenocarcinoma, forthemore, CDX-2 and LI-cadherin in the intestinal metaplasia gastric shown a strong relationship.
Conclusion: The abnormal expression of CDX-2 was correlated with early stag of GC, maybe it plays an anti-oncogene role in the development of gastric carcinoma. GCs with high CDX-2 index have low invasion,high differentiation ,and Detection of CDX-2 expression in gastric cancer tisues can be useful in the determination of malignancy and prognosis.The abnormal expression of LI-cadherin was correlated with intestinal metaplasia and gastric adenocarcinoma. GCs with high LI-cadherin index have more lymph node metastasis, The Detection of LI-cadherin expression in gastric cancer tissues can be useful in the determination of malignancy and prognosis.CDX-2 and LI-intestinal cadherine are specific markers, and two in the normal physiological circumstances expression in the small intestine and colon mucosa. This study shows that in gastric intestinal metaplasia and gastric adenocarcinoma in the CDX-2 LI-cadherine regulating the expression level, the latter being induced by the former, especially in the early stages of cancer occur, and they may be playing an important role in tumor promoter . Local cancer violations or distant metastasis often lead to treatment failure of the main reasons, the incidence of gastric cancer on the molecular mechanism of the biological behavior and the search for new anti-transfer measures is crucial.
方法:分别应用即用型鼠单克隆抗体(CDX2-88)和羊多克隆抗体(C-17,sc-6987)利用S-P免疫组化检测246例不同胃组织(包括正常胃黏膜30例、慢性浅表性胃炎30例、慢性萎缩性胃炎42例、肠化生胃黏膜58例、胃腺癌46例、癌旁组织30例、胃间质瘤10例) CDX-2与LI-cadherin蛋白的表达情况。
结果:CDX-2基因蛋白在正常胃黏膜及慢性胃炎中不表达;在肠化生组织中阳性表达率为91.4%(53/58);在胃癌组织中阳性表达率为80.4%(37/46),按Laurien分型,肠型胃癌中CDX-2蛋白阳性表达率高于弥漫型胃癌,并有显著性差异(P<0.050) ;CDX-2与细胞分化程度呈高度正相关(P<0.005),但与性别、年龄、浸润深度、胃癌分期及淋巴结转移无关。CDX-2在癌旁组织及胃间质瘤中无表达。LI-cadherin基因蛋白在正常胃黏膜及慢性胃炎中不表达;在肠化生组织中阳性表达率为83%(48/58);在胃腺癌组织中阳性表达率为65%(30/46),按Laurien分型,肠型胃癌中LI-cadherin蛋白阳性表达率(78%)高于弥漫型胃癌(35%),差异有统计学意义(P<0.050) ;LI-cadherin与淋巴结转移及临床分期明显正相关(P<0.010),在癌旁组织及胃间质瘤中无表达。CDX-2与LI-cadherin的过度表达紧密相关,而且CDX-2与LI-cadherin在肠化生胃黏膜中表现出很强的伴随关系。
结论: CDX-2的异常表达可能与胃癌的早期发生有关,且可能是一种抑癌基因,CDX-2高表达胃癌其侵袭性低,细胞分化程度高,因而检测其表达强度有助于判断胃癌恶性程度及胃癌患者的预后。LI-cadherin的异常表达与肠化生及胃腺癌的发生有关, LI-cadherin高表达者淋巴结转移率高,检测其表达强度有助于判断胃癌恶性程度及胃癌患者的预后。CDX-2和LI-cadherine均是肠特异性标记物,而且二者在正常生理情况下均表达于小肠和结肠黏膜。本项研究表明,在胃黏膜肠化生和胃腺癌中CDX-2调节LI-cadherine的表达水平,后者被前者所诱导,尤其是在癌组织发生的初期,二者可能扮重要促癌作用。癌细胞局部侵犯或发生远处转移常常是导致临床治疗失败的主要原因,因此研究胃癌发病的分子机制和生物学行为对于寻找新的抗转移措施是非常关键的。
Objective: CDX-2 and LI-cadherin in gastric cancer and precancerous lesions of the situation and in case of gastric cancer in epithelial expression and distribution are still unclear, through research the CDX-2 and LI-cadherin expression levels and distribution in gastric cancer, adjacent, normal gastric mucosa, Gastrointestinal stromal tumors, chronic gastritis and gastric intestinal metaplasia, and both the expression of different gender and the positive rate of gastric cancer patients in the expression of differences, and different Types of cancer, cell differentiation, metastasis of the depth of invasion of gastric cancer, gastric cancer Laurien stage and the relationship between the clinical stage, to studies the molecular mechanism of gastric cancer about the two factors in gastric cancer and precancerous lesions in the relationship between the exploration and gastric precancerous lesions.
Methods: In this study we examined the expression of caudal-related homeo box transcription factor 2(CDX-2) with monoclonal antibody(CDX2-88)and LI-cadherin with Goat polyclonal antibody(C-17,sc-6987) using SP immunohistochemical detection of 246 cases of various stomach.Including two hundred and forty six specimens were collected,including normal epithelia(n=30), chronic superficial gastritis (n=30), chronic atrophic gastritis(n=42) , intestinal metaplasia (n=58),gastric adenocarcinoma(n=46), nearing cancer(n=30), gastric stromal tumor(n=10).The expression of CDX-2 was detected in alI the tissues by immunohischemistry.
Results: The expression of CDX-2 in normaI epithelia and chronic gastritis are all negative , the positive rates of CDX-2 expresion in intestinal metaplasia and gastric adenocarcinoma are 91.4% and 80.4%,classification with Laurien, the positive rates of CDX-2 expresion in intestinal type and well-differentiated were higher than those in the diffuse type poorly differentiated (P<0.005).The expression of CDX-2 was independence of sex,age,depth of invasion, staging and lymph node metastasis. The nearing cancer and gastric stromal tumor exhibited negative CDX-2 expression.The expression of LI-cadherin in normaI epithelia and chronic gastritis are all negative , the positive rates of LI-cadherin expresion in intestinal metaplasia and gastric adenocarcinoma are 83 % (48/58) and 65 %(30/46),classification with Laurien, the positive rates of LI-cadherin expresion in intestinal type were higher(78%) than those in the diffuse type (35%) (P<0.050).LI-cadherin is positive correlation with lymph node metastasis and staging. The nearing cancer and gastric stromal tumor exhibited negative LI-cadherin expression. LI-cadherin expression closely related to the excessive of CDX-2 in gastric adenocarcinoma, forthemore, CDX-2 and LI-cadherin in the intestinal metaplasia gastric shown a strong relationship.
Conclusion: The abnormal expression of CDX-2 was correlated with early stag of GC, maybe it plays an anti-oncogene role in the development of gastric carcinoma. GCs with high CDX-2 index have low invasion,high differentiation ,and Detection of CDX-2 expression in gastric cancer tisues can be useful in the determination of malignancy and prognosis.The abnormal expression of LI-cadherin was correlated with intestinal metaplasia and gastric adenocarcinoma. GCs with high LI-cadherin index have more lymph node metastasis, The Detection of LI-cadherin expression in gastric cancer tissues can be useful in the determination of malignancy and prognosis.CDX-2 and LI-intestinal cadherine are specific markers, and two in the normal physiological circumstances expression in the small intestine and colon mucosa. This study shows that in gastric intestinal metaplasia and gastric adenocarcinoma in the CDX-2 LI-cadherine regulating the expression level, the latter being induced by the former, especially in the early stages of cancer occur, and they may be playing an important role in tumor promoter . Local cancer violations or distant metastasis often lead to treatment failure of the main reasons, the incidence of gastric cancer on the molecular mechanism of the biological behavior and the search for new anti-transfer measures is crucial.
引文
1. Boring CC, Squires TS, Tong T, et al. Cancer statistics. CA Cancer J Clin 1994; 44:7-26
2. Samuel Ko,Kent MC,John ,et al.CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach[J]. Journa of Pathology. 2005;205:615-622.
3. Hinoi T, Lucas P, Kuick R, et al. CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithetium and intestinal metaplasia[J]. Gastroenterology 2002;123:1565-1577
4. McGinnis W,Krumlauf R. Homebox genes and axial patterning[J].Cell 1992; 68:283-302
5. Li MK, Folpe AL. CDX-2, a new marker for adenocarcinoma of gastrointestinal origin. Adv Anat Pathol[J],2004,11:101-105.
6. Werling R,Yaziji H,Bacchi cE,et al.cDx2,a Highly sensitive and specific marker of adenocarcinomas of intestin al origin:An immunohistochemical survey of 476 primary and metastatic carcinomas[J].Am SurPathof 2003;27:303—310.
7. Barbara AM,Jean EC,M,et al. Helicobacter pylori regulates the expression of inhibitors of DNA binding (Id) proteins by gastric epithetial cells [J].Microbes and Infection . 2006; 8:1064-1074
8. Seno H, Oshima M, Taniguchi MA, et al. CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer[J]. Prognostic implications. Int J Oncol ,2002;21:769–774
9. Fukamachi H, Ito K, Ito Y. Runx3-/- gastric epithelial cells differentiate into intestinal type cells[J]. Biochem Biophys Res Commun,2004;321:58–64.
10. Grotzinger C,Kneifel J,Patschan D, et al. LI-cadherin :a marker of gastric metaplasia and neoplasmia[ J ]. Gut 2001;49:73-81
11. Phillips RW, Frierson HF, Moskaluk CA. Cdx2 as a marker of epithelial intestinal differentiation in the esophagus[J]. Am J Surg Pathol 2003; 27: 1442-1447.
12. Yamamoto H, Bai YQ, Yuasa Y. Homeodomain protein CDX2 regulates goblet-specific MUC2 gene expression[J]. Biochem Biophys Res Commun 2003;300:813–818.
13. Tatematsu M, Tsukamoto T, Inada K .Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia[J]. Cancer Sci ,2003;94:135–141
14. Satoh K, Mutoh H, Eda A, et al.Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: effect of eradication of Helicobacterpylori [J]. Helicobacter , 2002; 7:192–198.
15. Bai YQ, Miyake S, Iwai T, et al.CDX2, a homeobox transcription factor, upregulates transcription of p21/WAF1/CIP1 [J], Oncogene , 2003;22:7942-7949.
16. Yuasa Y, Nagasaki H, Akiyama Y, et al. Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients [J]. Carcinogenesis 2005;26:193–200.
17. Almeida R,Silva E,Santos-Silva F,et al.Expression of intestine-specific transcription factors, CDX1 and CDX2,in intestinel metaplasia and gastric carcinomas [J].J Pathol , 2003; 199:36-40
18. Kristina Roessler,Stefan P Monig,Paul M,et al.Co-expression of CDX2 and MUC2 in gastric carcinomas:Correlations with clinic-pathological parameters and prognosis [J].World Gastroenterol, 2005;11(21):3182-3188
19. Mizoshita T, Tsukamoto T.Expression of CDX2 and the phenol of advanced gastric cancers:relationship with prognosis [J]. J Cancer Res Clin Oncol,2003;129: 727-734
20. Overduin M ,Harvey TS.Bagby S,et a1.Soution structure of the epithe1ial cadherin domain responsible for selective cel1 adhesion [J]. Science,1995;267:386～390
21. Takeichi M. Cadherins in cancer: implications for invasion and metastasis[J]. Curr Opin Cell Biol .1993; 5:806-811
22. Perl AK, Wilgenbus P, Dahl U, et al. A causal role for E-cadherin in for the transition from adenoma to carcinoma[J]. Nature .1993;392:190-193
23. Kyong,Ah Yoon, Ja-Lok Ku,et al. Germline mutateons of E-cadherin gene in Korean familial gastric cancer patients[J]. J Hum Genet.1999;44:177-180
24. Bemdorff, D,Gessner, R, Kreft,B, et al. Liver-intestine cadherin : molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine [ J ]. The Journal of Cell Biology. 1994;125(6): 1353-1369
25. Kreft B, Berndorff D, Bottinger A,et al. LI-Cadherin-mediated Cell-Cell Adhersion Does Not Require Cytoplasmic Interactions[ J ].The Journal of Biology, 1997; 136(5):1109-1121
26. Samuel Ko, Kent-Man Chu, John M.Luk, et al. Overexpression of LI-cadherin in gastric cancer is associated with lymph node metasis[J]. Biochemical and Biophysical Research Communications. 2004;319:562-568
27. Reiko Ito,Naohide Oue,Kazuhiro Yoshida, et al. Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer[J].Virchows Arch 2005:1-6
1 Bremnes RM,Veve R,Gabrielson E, et al.High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. J Clin Oncol, 2002,20(10):2417-2428.
2 Bing-Jing Wang,Zhi-Qian Zhang,Yang Ke.Conversion of cadherin isoforms in cultured human gastric carcinoma cells.World J Gastroenlerol 2006 February 14;12(6):966-970.
3 Bae SH , J ung ES , Park YM , et al. Expression patterns of E-cadherin and beta-catenin according to clinicopathological characteristics of hepatocellular carcinoma. Taehan KanHakhoe Chi , 2002 , 8 (3) : 297-303.
4 Nakajima M ,Fukuchi M ,Miyazaki T ,et al. Reduced expression of Axin correlates with tumour progression of oesophageal squamous cell carcinoma. Br J Cancer ,2003 ,88 (11) :1734-1739.
5 Kimura Y,Fumhata T.Frequent beta-eatenin alteration in gallbladder eareinomas[Jld Exp Clin Cancer Res,2003,22(2):321.
6 Ku JL,Yoon KA.Establishment and eharacterisafion of six human biliary tract cancer cell llnes[J1.Br J Cancer,2002。87(2):187.
7 Choi YL,XIlaII YH.An iramunohistochemical study of the expression of adhesion molecules in gallbladder lesions[j]d Histochem Cytochem,2004,52(5):591.
8 林英城,吴名耀,李德锐,吴贤英,郑瑞明.E-cadherin 及其相关蛋白在食管鳞癌的表达与预后的关系.肿瘤防治研究[J],2003,30(2):112-114.
9 张秀凤,王益民,王瑞,魏丽珍,李琰,郭炜.E-钙黏蛋白基因多态性与食管、贲门癌的关系.癌症[J],2005,24(5):513-519.
10 heng ZH,Sun XJ, Ma MC , et al.Studies of promoter methylation status and protein expression of E-cadherin gene in associated progression stages of gastric cancer.Yi Chuan Xue Bao,2003, 30(2):103-108.
11 Li Wang,Fan Zhang,Ping-Ping Wu,et al.Eisordered beta-catenin expression and E-cadherin/CDH1 promoter methylation in gastric carcinoma.World Gastroenterol,2006 July 14;12(26):42298-4231.
12 Zullo A, Romiti A,Borrini F, et al.Alteration of E-cadherin expression in gastric mucosa:role of intestinal metaplasia and Helicobacter pylori infection. Anticancer Res , 2004,24 (3a):1603-1607.
13 Nakamura E,Sugihara H,Bamba M,et al.Dynamic alteration of the E-cadherin/catenin complex during cell differentiation and invasion of undifferentiated-type gastric carcinomas. J Pathol, 2005, 205 (3) :349-358.
14 A.Schwarz.Preventive gastrectomy in patients with gastric cancer risk due to genetic alterations of the E-cadherin gene defect.LANGENBECKS Arch Surg,2003,388:27-32.
15 Carla Oliveira,Herculano MOReira,Raquel Seruca.Role of pathology in the identification of hereditary diffuse gastric cancer:report of a Portuguese family.Virchows Arch(2005)446:181-184.
16 Kyong-Ah Yoon,Ja-Lok Ku,Han-Kwang Yang,et al.Germline mutations of E-cadherin gene in Kouean familial gastric cancer patients.J Hum Genet ,1999 ,44:177-180.
17 Lowy AM,张志功,朱化刚.恢复E2钙黏蛋白和β2连接素的表达通过诱导细胞凋亡抑制胰腺癌细胞的生长. 国外医学:肿瘤学分册.2002 ,132 (2) : 141～148.
18 Kang GH,Lee HJ,Hwang KS,et al.Aberrant CpG island hypermethylation of chromicgastretis,in relation to aging,gender,intestinal metaplasia, and chronic inflammation.Am J Pathol,2003, 163(4):1551-1556.
19 Zheng ZH,Sun XJ,Ma MC,et al.Studies of promoter methylation status and protein expressionof E-cadherin gene in associated progression stages of gastric cancer.Yi Chuan Xue Bao,2003,30 (2):103-108.
1 . Li MK, Folpe AL. CDX-2, a new marker for adenocarcinoma of gastrointestinal origin. Adv Anat Pathol[J],2004,11:101-105.
2. Werling Rw,Yaziji H,Bacchi cE,et al.cDx2,a Highly sensitive and specific marker of adenocarcinomas of intestin al origin:An immunohistochemical survey of 476 primary and metastatic carcinomas[J].Am SurPathof 2003;27:303—310.
3. Tamai Y, Nakajima R, Ishikawa T, et al. Colonic hamartoma development by anomalousduplication in Cdx2 knockout mice[J]. Cancer Res1999;59:2965-297
4. Chaweng K,James R,Hammond VE,et al.Homeosis and intestinel tumours in Cdx2 mutant mice[J].Nature 1997;386:84-87
5. Phillips RW, Frierson HF Jr, Moskaluk CA. Cdx2 as a marker of epithelial intestinal differentiation in the esophagus[J]. Am J Surg Pathol 2003; 27: 1442-1447.
6. Tsutomu M,Ken-ichi I,Tetsuya T,et al.Expression of the intestine-specific transcription factors,Cdx1 and Cdx2, correlates shift to an intestinel phenol in gastric cancer cells[J]. Cancer Res Clin Oncol. 2004:130:29-36
7. Seno H, Oshima M, Taniguchi MA, et al. CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer[J]. Prognostic implications. Int J Oncol ,2002;21:769–774
8 . Tersuya T,Tsutomu M,Masae T.Gastric-and-intestinal mixed-type intestinel metaplasia:aberrant expression of transcription factors and stem cell intestinelization[J].International and Japanese Gastric Cancer Associations.2006;9:156-166
9. Fukamachi H, Ito K, Ito Y. Runx3-/- gastric epithelial cells differentiate into intestinal type cells[J]. Biochem Biophys Res Commun,2004;321:58–64.
10. KIM,HYUNG-SEOK,LEE,et al.CDX-2 homeobox gene expression in human gastric carcinoma and precursor lesions[J].Journal of Gastroenterology and Hepatology,2006;21(2):438-442
11 . Yamamoto H, Bai YQ, Yuasa Y. Homeodomain protein CDX2 regulates goblet-specific MUC2 gene expression[J]. Biochem Biophys Res Commun 2003;300:813–8.
12. Yuasa Y, Nagasaki H, Akiyama Y, et al. Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients [J]. Carcinogenesis 2005;26:193–200.
13 . Yamamoto H, Bai YQ, Yuasa Y .Homeodomain protein CDX2 regulates goblet-speciWc MUC2 gene expression[J]. Biochem Biophys Res Commun ,2003;300:813–818
14. Tatematsu M, Tsukamoto T, Inada K .Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia[J]. Cancer Sci ,2003;94:135–141
15. Barbara Ada Manzo,Jean E.Crabtree,M,et al. Helicobacter pylori regulates the expression of inhibitors of DNA binding (Id) proteins by gastric epithetial cells [J].Microbes and Infection . 2006; 8:1064-1074
16. Y.Q. Bai, S. Miyake, T. Iwai, et al.CDX2, a homeobox transcription factor, upregulates transcription of p21/WAF1/CIP1 [J], Oncogene , 2003;22:7942-7949.
17. Satoh K, Mutoh H, Eda A, et al.Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: effect of eradication of Helicobacter pylori [J]. Helicobacter , 2002; 7:192–8.
18. Almeida R,Silva E,Santos-Silva F,et al.Expression of intestine-specific transcription factors,CDX1 and CDX2,in intestinel metaplasia and gastric carcinomas [J].J Pathol , 2003; 199:36-40
19. Ko S, Chu KM, Luk JM,et al. CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia andadenocarcinoma of the stomach [J]. J Pathol 2005;205:615-622
20. Yuasa Y, Nagasaki H, Akiyama Y, et al. Relationship between CDX-2 gene methylation and dietary factors in gastric cancer patients [J]. Carcinogenesis ,2005; 26:193-200
21. Mutoh H, Sakurai S, Satoh K, et al. Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic mice [J]. Cancer Res ,2004; 64: 7740–7747.
22. Mizoshita T, Tsukamoto T, Inada K, et al. Immunohistochemically detectable Cdx-2 ispresent in intestinal phenotypic elements in early gastric cancers of both differentiated and undifferentiated types, with no correlation to nonneoplastic surrounding mucosa [J]. Pathol Int, 2004;54:392-400
23. Tautomu Mizoshita,Tetsuya Tsukamoto, et al.Expression of CDX2 and the phenol of advanced gastric cancers:relationship with prognosis [J]. J Cancer Res Clin Oncol,2003;129: 727-734
24. Seno H,Oshima M,Taniguchi MA,et al.CDX2 expression in the stomach with intestinel metaplasia and intestinal-type cancer:Prognostic implications [J].Int J Oncol ,2002;21:769-774
25. Yamamoto H,Bai YQ,Yuasa Y.Homeodomain protein CDX2 regulates goblet-specific MUC2gene expression [J].Biochem Biophys Res Commun ,2003;300:813-818
26. Kristina Roessler,Stefan P Monig,Paul M,et al.Co-expression of CDX2 and MUC2 in gastric carcinomas :Correlations with clinic-pathological parameters and prognosis [J].World Gastroenterol, 2005;11(21):3182-3188
27. Eda A, Osawa H, Satoh K, et al. Aberrant expression of CDX2 in Barrett’s epithelium and inXammatory esophageal mucosa (2003). J Gastroenterol ,2003;38:14–22
28. Samuel Ko,Kent-Man Chu,John ,et al.CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach[J].Journa of Pathology. 2005;205:615-622.
29 . Li MK, Folpe AL. CDX-2, a new marker for adenocarcinoma of gastrointestinal origin [J]. Adv Anat Pathol,2004,11:101-105
30. Werling RW, Yaziji H, Bacchi CE, et al. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of
476 primary and metastatic carcinomas[J].Am J Surg Pathol ,2003; 27: 303-10.
1. Overduin M ,Harvey TS.Bagby S,et a1.Soution structure of the epithe1ial cadherin domain responsible for selective cel1 adhesion [ J ]. Science,1995;267:386～390
2. Jacobs, K.A., Collins-Racie, L.A., et al. A genetic selection for isolating cDNAs encoding secreted proteins [ J ]. Gene .1997;198:289-296
3. Julia Horsfield, Anassuya Ramachandran, Katja Reuter, et al. Cadherin-17 is required to maintain pronephric duct integrity during zebrafish development [J]. Mechanisms of Development. 2002;115:15-26
4. M.W.Wendeler , R.Jung, H.Himmelbauer, et al. Unique gene structure and paralogy define the 7D-cadherin family [J].Scllular and Molecular Life Sciences,2006:1~10
5. Kremmidiotis, G., Baker, E., Crawford, J., et al. Localization of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity[J]. Genomics 1998; 49, 467–471
6 Crosier, P.S., Bardsley, A., Horsfield, J.A., et al . An in situ hybridization screen in zebrafish for the selection of genes encoding secreted proteins[ J ]. Dev. Dyn. 2002; 222: 637–644
7. Bemdorff,-D,Gessner,-R, Kreft,B, et al. Liver-intestine cadherin : molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine [ J ]. The Journal of Cell Biology. 1994;125(6): 1353-1369
8. Gessner R, Tauber R. Intestinal cell adhersion molecules.Liver-intestine cadherin[ J ]. Ann N Y Acad Sci 2000;915;136-143
9. R.Jung, M.W.Wendeler, M.Danevad,et al. Phylogenetic origin of LI-cadherin revealed by protein and gene structure analysis[ J ]. CMLS.Cell.Mol.Life Sci.2004;61:1157-1166
10. Bremnes RM,Veve R,Gabrielson E, et al.High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer[ J ]. J Clin Oncol, 2002,20(10):2417-2428
11. Bertolt Kreft, Dietmar Berndorff, Anja Bottinger,et al. LI-Cadherin-mediated Cell-Cell Adhersion Does Not Require Cytoplasmic Interactions[ J ].The Journal of Biology, 1997; 136(5):1109-1121
12. Nakamura E,Sugihara H,Bamba M,et al.Dynamic alteration of the E-cadherin/catenin complex during cell differentiation and invasion of undifferentiated-type gastric carcinomas [ J ]. J Pathol, 2005; 205 (3) :349-358
13. Boring CC, Squires TS, Tong T, et al. Cancer statistics. CA Cancer J Clin 1994;44:7-26
14. Takeichi M. Cadherins in cancer: implications for invasion and metastasis[ J ]. CurrOpin Cell Biol .1993; 5:806-811
15. Perl AK, Wilgenbus P, Dahl U, et al. A causal role for E-cadherin in for the transition from adenoma to carcinoma[ J ]. Nature .1993;392:190-193
16. Guilford P,Hopkins J, Harraway J,McLeod M, et al. E-cadherin gremlin mutateons in familial gastric cancer.Nature 1993;392:402-405
17.Kyong,Ah Yoon, Ja-Lok Ku,et al. Germline mutateons of E-cadherin gene in Korean familial gastric cancer patients[ J ]. J Hum Genet.1999;44:177-180
18. Samuel Ko, Kent-Man Chu, John M.Luk, et al. Overexpression of LI-cadherin in gastric cancer is associated with lymph node metasis[ J ]. Biochemical and Biophysical Research Communications. 2004;319:562-568
19. Grotzinger C,Kneifel J,Patschan D, et al. LI-cadherin :a marker of gastric metaplasia and neoplasmia[ J ]. Gut 2001;49:73-81
20. Reiko Ito,Naohide Oue,Kazuhiro Yoshida, et al. Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer[J].Virchows Arch 2005:1-6
21. Chan AO, Lam SK, Chu KM, et al. Soluble E-cadherin is a valid prognostic marker in gastric carcinoma[ J ]. Gut 2001; 48:808-811
22. Chan AO, Chu KM, Lam SK, et al. Soluble E-cadherin is an independent prêtherapeutic factor for long-term survival in gastric cancer[ J ]. J Clin Oncol 2003;21:2288-2293
23 . McGinnis W,Krumlauf R. Homebox genes and axial patterning[ J ].Cell 1992;68:283-302
24. Hinoi T, Lucas PC, Kuick R, et al.CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithetium and intestinal metaplasia[ J ]. Gastroenterology 2002;123:1565-1577
25.Samuel Ko,Kent-Man Chu,John Moon-ching Luk, et al. CDX2 co-localizes with liver-intestine cadherin in intestinel metaplasia and adenocarcinoma of the stomach[ J ].Journal of Pathology. 2005;205:615-622
2. Samuel Ko,Kent MC,John ,et al.CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach[J]. Journa of Pathology. 2005;205:615-622.
3. Hinoi T, Lucas P, Kuick R, et al. CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithetium and intestinal metaplasia[J]. Gastroenterology 2002;123:1565-1577
4. McGinnis W,Krumlauf R. Homebox genes and axial patterning[J].Cell 1992; 68:283-302
5. Li MK, Folpe AL. CDX-2, a new marker for adenocarcinoma of gastrointestinal origin. Adv Anat Pathol[J],2004,11:101-105.
6. Werling R,Yaziji H,Bacchi cE,et al.cDx2,a Highly sensitive and specific marker of adenocarcinomas of intestin al origin:An immunohistochemical survey of 476 primary and metastatic carcinomas[J].Am SurPathof 2003;27:303—310.
7. Barbara AM,Jean EC,M,et al. Helicobacter pylori regulates the expression of inhibitors of DNA binding (Id) proteins by gastric epithetial cells [J].Microbes and Infection . 2006; 8:1064-1074
8. Seno H, Oshima M, Taniguchi MA, et al. CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer[J]. Prognostic implications. Int J Oncol ,2002;21:769–774
9. Fukamachi H, Ito K, Ito Y. Runx3-/- gastric epithelial cells differentiate into intestinal type cells[J]. Biochem Biophys Res Commun,2004;321:58–64.
10. Grotzinger C,Kneifel J,Patschan D, et al. LI-cadherin :a marker of gastric metaplasia and neoplasmia[ J ]. Gut 2001;49:73-81
11. Phillips RW, Frierson HF, Moskaluk CA. Cdx2 as a marker of epithelial intestinal differentiation in the esophagus[J]. Am J Surg Pathol 2003; 27: 1442-1447.
12. Yamamoto H, Bai YQ, Yuasa Y. Homeodomain protein CDX2 regulates goblet-specific MUC2 gene expression[J]. Biochem Biophys Res Commun 2003;300:813–818.
13. Tatematsu M, Tsukamoto T, Inada K .Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia[J]. Cancer Sci ,2003;94:135–141
14. Satoh K, Mutoh H, Eda A, et al.Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: effect of eradication of Helicobacterpylori [J]. Helicobacter , 2002; 7:192–198.
15. Bai YQ, Miyake S, Iwai T, et al.CDX2, a homeobox transcription factor, upregulates transcription of p21/WAF1/CIP1 [J], Oncogene , 2003;22:7942-7949.
16. Yuasa Y, Nagasaki H, Akiyama Y, et al. Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients [J]. Carcinogenesis 2005;26:193–200.
17. Almeida R,Silva E,Santos-Silva F,et al.Expression of intestine-specific transcription factors, CDX1 and CDX2,in intestinel metaplasia and gastric carcinomas [J].J Pathol , 2003; 199:36-40
18. Kristina Roessler,Stefan P Monig,Paul M,et al.Co-expression of CDX2 and MUC2 in gastric carcinomas:Correlations with clinic-pathological parameters and prognosis [J].World Gastroenterol, 2005;11(21):3182-3188
19. Mizoshita T, Tsukamoto T.Expression of CDX2 and the phenol of advanced gastric cancers:relationship with prognosis [J]. J Cancer Res Clin Oncol,2003;129: 727-734
20. Overduin M ,Harvey TS.Bagby S,et a1.Soution structure of the epithe1ial cadherin domain responsible for selective cel1 adhesion [J]. Science,1995;267:386～390
21. Takeichi M. Cadherins in cancer: implications for invasion and metastasis[J]. Curr Opin Cell Biol .1993; 5:806-811
22. Perl AK, Wilgenbus P, Dahl U, et al. A causal role for E-cadherin in for the transition from adenoma to carcinoma[J]. Nature .1993;392:190-193
23. Kyong,Ah Yoon, Ja-Lok Ku,et al. Germline mutateons of E-cadherin gene in Korean familial gastric cancer patients[J]. J Hum Genet.1999;44:177-180
24. Bemdorff, D,Gessner, R, Kreft,B, et al. Liver-intestine cadherin : molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine [ J ]. The Journal of Cell Biology. 1994;125(6): 1353-1369
25. Kreft B, Berndorff D, Bottinger A,et al. LI-Cadherin-mediated Cell-Cell Adhersion Does Not Require Cytoplasmic Interactions[ J ].The Journal of Biology, 1997; 136(5):1109-1121
26. Samuel Ko, Kent-Man Chu, John M.Luk, et al. Overexpression of LI-cadherin in gastric cancer is associated with lymph node metasis[J]. Biochemical and Biophysical Research Communications. 2004;319:562-568
27. Reiko Ito,Naohide Oue,Kazuhiro Yoshida, et al. Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer[J].Virchows Arch 2005:1-6
1 Bremnes RM,Veve R,Gabrielson E, et al.High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer. J Clin Oncol, 2002,20(10):2417-2428.
2 Bing-Jing Wang,Zhi-Qian Zhang,Yang Ke.Conversion of cadherin isoforms in cultured human gastric carcinoma cells.World J Gastroenlerol 2006 February 14;12(6):966-970.
3 Bae SH , J ung ES , Park YM , et al. Expression patterns of E-cadherin and beta-catenin according to clinicopathological characteristics of hepatocellular carcinoma. Taehan KanHakhoe Chi , 2002 , 8 (3) : 297-303.
4 Nakajima M ,Fukuchi M ,Miyazaki T ,et al. Reduced expression of Axin correlates with tumour progression of oesophageal squamous cell carcinoma. Br J Cancer ,2003 ,88 (11) :1734-1739.
5 Kimura Y,Fumhata T.Frequent beta-eatenin alteration in gallbladder eareinomas[Jld Exp Clin Cancer Res,2003,22(2):321.
6 Ku JL,Yoon KA.Establishment and eharacterisafion of six human biliary tract cancer cell llnes[J1.Br J Cancer,2002。87(2):187.
7 Choi YL,XIlaII YH.An iramunohistochemical study of the expression of adhesion molecules in gallbladder lesions[j]d Histochem Cytochem,2004,52(5):591.
8 林英城,吴名耀,李德锐,吴贤英,郑瑞明.E-cadherin 及其相关蛋白在食管鳞癌的表达与预后的关系.肿瘤防治研究[J],2003,30(2):112-114.
9 张秀凤,王益民,王瑞,魏丽珍,李琰,郭炜.E-钙黏蛋白基因多态性与食管、贲门癌的关系.癌症[J],2005,24(5):513-519.
10 heng ZH,Sun XJ, Ma MC , et al.Studies of promoter methylation status and protein expression of E-cadherin gene in associated progression stages of gastric cancer.Yi Chuan Xue Bao,2003, 30(2):103-108.
11 Li Wang,Fan Zhang,Ping-Ping Wu,et al.Eisordered beta-catenin expression and E-cadherin/CDH1 promoter methylation in gastric carcinoma.World Gastroenterol,2006 July 14;12(26):42298-4231.
12 Zullo A, Romiti A,Borrini F, et al.Alteration of E-cadherin expression in gastric mucosa:role of intestinal metaplasia and Helicobacter pylori infection. Anticancer Res , 2004,24 (3a):1603-1607.
13 Nakamura E,Sugihara H,Bamba M,et al.Dynamic alteration of the E-cadherin/catenin complex during cell differentiation and invasion of undifferentiated-type gastric carcinomas. J Pathol, 2005, 205 (3) :349-358.
14 A.Schwarz.Preventive gastrectomy in patients with gastric cancer risk due to genetic alterations of the E-cadherin gene defect.LANGENBECKS Arch Surg,2003,388:27-32.
15 Carla Oliveira,Herculano MOReira,Raquel Seruca.Role of pathology in the identification of hereditary diffuse gastric cancer:report of a Portuguese family.Virchows Arch(2005)446:181-184.
16 Kyong-Ah Yoon,Ja-Lok Ku,Han-Kwang Yang,et al.Germline mutations of E-cadherin gene in Kouean familial gastric cancer patients.J Hum Genet ,1999 ,44:177-180.
17 Lowy AM,张志功,朱化刚.恢复E2钙黏蛋白和β2连接素的表达通过诱导细胞凋亡抑制胰腺癌细胞的生长. 国外医学:肿瘤学分册.2002 ,132 (2) : 141～148.
18 Kang GH,Lee HJ,Hwang KS,et al.Aberrant CpG island hypermethylation of chromicgastretis,in relation to aging,gender,intestinal metaplasia, and chronic inflammation.Am J Pathol,2003, 163(4):1551-1556.
19 Zheng ZH,Sun XJ,Ma MC,et al.Studies of promoter methylation status and protein expressionof E-cadherin gene in associated progression stages of gastric cancer.Yi Chuan Xue Bao,2003,30 (2):103-108.
1 . Li MK, Folpe AL. CDX-2, a new marker for adenocarcinoma of gastrointestinal origin. Adv Anat Pathol[J],2004,11:101-105.
2. Werling Rw,Yaziji H,Bacchi cE,et al.cDx2,a Highly sensitive and specific marker of adenocarcinomas of intestin al origin:An immunohistochemical survey of 476 primary and metastatic carcinomas[J].Am SurPathof 2003;27:303—310.
3. Tamai Y, Nakajima R, Ishikawa T, et al. Colonic hamartoma development by anomalousduplication in Cdx2 knockout mice[J]. Cancer Res1999;59:2965-297
4. Chaweng K,James R,Hammond VE,et al.Homeosis and intestinel tumours in Cdx2 mutant mice[J].Nature 1997;386:84-87
5. Phillips RW, Frierson HF Jr, Moskaluk CA. Cdx2 as a marker of epithelial intestinal differentiation in the esophagus[J]. Am J Surg Pathol 2003; 27: 1442-1447.
6. Tsutomu M,Ken-ichi I,Tetsuya T,et al.Expression of the intestine-specific transcription factors,Cdx1 and Cdx2, correlates shift to an intestinel phenol in gastric cancer cells[J]. Cancer Res Clin Oncol. 2004:130:29-36
7. Seno H, Oshima M, Taniguchi MA, et al. CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer[J]. Prognostic implications. Int J Oncol ,2002;21:769–774
8 . Tersuya T,Tsutomu M,Masae T.Gastric-and-intestinal mixed-type intestinel metaplasia:aberrant expression of transcription factors and stem cell intestinelization[J].International and Japanese Gastric Cancer Associations.2006;9:156-166
9. Fukamachi H, Ito K, Ito Y. Runx3-/- gastric epithelial cells differentiate into intestinal type cells[J]. Biochem Biophys Res Commun,2004;321:58–64.
10. KIM,HYUNG-SEOK,LEE,et al.CDX-2 homeobox gene expression in human gastric carcinoma and precursor lesions[J].Journal of Gastroenterology and Hepatology,2006;21(2):438-442
11 . Yamamoto H, Bai YQ, Yuasa Y. Homeodomain protein CDX2 regulates goblet-specific MUC2 gene expression[J]. Biochem Biophys Res Commun 2003;300:813–8.
12. Yuasa Y, Nagasaki H, Akiyama Y, et al. Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients [J]. Carcinogenesis 2005;26:193–200.
13 . Yamamoto H, Bai YQ, Yuasa Y .Homeodomain protein CDX2 regulates goblet-speciWc MUC2 gene expression[J]. Biochem Biophys Res Commun ,2003;300:813–818
14. Tatematsu M, Tsukamoto T, Inada K .Stem cells and gastric cancer: role of gastric and intestinal mixed intestinal metaplasia[J]. Cancer Sci ,2003;94:135–141
15. Barbara Ada Manzo,Jean E.Crabtree,M,et al. Helicobacter pylori regulates the expression of inhibitors of DNA binding (Id) proteins by gastric epithetial cells [J].Microbes and Infection . 2006; 8:1064-1074
16. Y.Q. Bai, S. Miyake, T. Iwai, et al.CDX2, a homeobox transcription factor, upregulates transcription of p21/WAF1/CIP1 [J], Oncogene , 2003;22:7942-7949.
17. Satoh K, Mutoh H, Eda A, et al.Aberrant expression of CDX2 in the gastric mucosa with and without intestinal metaplasia: effect of eradication of Helicobacter pylori [J]. Helicobacter , 2002; 7:192–8.
18. Almeida R,Silva E,Santos-Silva F,et al.Expression of intestine-specific transcription factors,CDX1 and CDX2,in intestinel metaplasia and gastric carcinomas [J].J Pathol , 2003; 199:36-40
19. Ko S, Chu KM, Luk JM,et al. CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia andadenocarcinoma of the stomach [J]. J Pathol 2005;205:615-622
20. Yuasa Y, Nagasaki H, Akiyama Y, et al. Relationship between CDX-2 gene methylation and dietary factors in gastric cancer patients [J]. Carcinogenesis ,2005; 26:193-200
21. Mutoh H, Sakurai S, Satoh K, et al. Development of gastric carcinoma from intestinal metaplasia in Cdx2-transgenic mice [J]. Cancer Res ,2004; 64: 7740–7747.
22. Mizoshita T, Tsukamoto T, Inada K, et al. Immunohistochemically detectable Cdx-2 ispresent in intestinal phenotypic elements in early gastric cancers of both differentiated and undifferentiated types, with no correlation to nonneoplastic surrounding mucosa [J]. Pathol Int, 2004;54:392-400
23. Tautomu Mizoshita,Tetsuya Tsukamoto, et al.Expression of CDX2 and the phenol of advanced gastric cancers:relationship with prognosis [J]. J Cancer Res Clin Oncol,2003;129: 727-734
24. Seno H,Oshima M,Taniguchi MA,et al.CDX2 expression in the stomach with intestinel metaplasia and intestinal-type cancer:Prognostic implications [J].Int J Oncol ,2002;21:769-774
25. Yamamoto H,Bai YQ,Yuasa Y.Homeodomain protein CDX2 regulates goblet-specific MUC2gene expression [J].Biochem Biophys Res Commun ,2003;300:813-818
26. Kristina Roessler,Stefan P Monig,Paul M,et al.Co-expression of CDX2 and MUC2 in gastric carcinomas :Correlations with clinic-pathological parameters and prognosis [J].World Gastroenterol, 2005;11(21):3182-3188
27. Eda A, Osawa H, Satoh K, et al. Aberrant expression of CDX2 in Barrett’s epithelium and inXammatory esophageal mucosa (2003). J Gastroenterol ,2003;38:14–22
28. Samuel Ko,Kent-Man Chu,John ,et al.CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach[J].Journa of Pathology. 2005;205:615-622.
29 . Li MK, Folpe AL. CDX-2, a new marker for adenocarcinoma of gastrointestinal origin [J]. Adv Anat Pathol,2004,11:101-105
30. Werling RW, Yaziji H, Bacchi CE, et al. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of
476 primary and metastatic carcinomas[J].Am J Surg Pathol ,2003; 27: 303-10.
1. Overduin M ,Harvey TS.Bagby S,et a1.Soution structure of the epithe1ial cadherin domain responsible for selective cel1 adhesion [ J ]. Science,1995;267:386～390
2. Jacobs, K.A., Collins-Racie, L.A., et al. A genetic selection for isolating cDNAs encoding secreted proteins [ J ]. Gene .1997;198:289-296
3. Julia Horsfield, Anassuya Ramachandran, Katja Reuter, et al. Cadherin-17 is required to maintain pronephric duct integrity during zebrafish development [J]. Mechanisms of Development. 2002;115:15-26
4. M.W.Wendeler , R.Jung, H.Himmelbauer, et al. Unique gene structure and paralogy define the 7D-cadherin family [J].Scllular and Molecular Life Sciences,2006:1~10
5. Kremmidiotis, G., Baker, E., Crawford, J., et al. Localization of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity[J]. Genomics 1998; 49, 467–471
6 Crosier, P.S., Bardsley, A., Horsfield, J.A., et al . An in situ hybridization screen in zebrafish for the selection of genes encoding secreted proteins[ J ]. Dev. Dyn. 2002; 222: 637–644
7. Bemdorff,-D,Gessner,-R, Kreft,B, et al. Liver-intestine cadherin : molecular cloning and characterization of a novel Ca(2+)-dependent cell adhesion molecule expressed in liver and intestine [ J ]. The Journal of Cell Biology. 1994;125(6): 1353-1369
8. Gessner R, Tauber R. Intestinal cell adhersion molecules.Liver-intestine cadherin[ J ]. Ann N Y Acad Sci 2000;915;136-143
9. R.Jung, M.W.Wendeler, M.Danevad,et al. Phylogenetic origin of LI-cadherin revealed by protein and gene structure analysis[ J ]. CMLS.Cell.Mol.Life Sci.2004;61:1157-1166
10. Bremnes RM,Veve R,Gabrielson E, et al.High-throughput tissue microarray analysis used to evaluate biology and prognostic significance of the E-cadherin pathway in non-small-cell lung cancer[ J ]. J Clin Oncol, 2002,20(10):2417-2428
11. Bertolt Kreft, Dietmar Berndorff, Anja Bottinger,et al. LI-Cadherin-mediated Cell-Cell Adhersion Does Not Require Cytoplasmic Interactions[ J ].The Journal of Biology, 1997; 136(5):1109-1121
12. Nakamura E,Sugihara H,Bamba M,et al.Dynamic alteration of the E-cadherin/catenin complex during cell differentiation and invasion of undifferentiated-type gastric carcinomas [ J ]. J Pathol, 2005; 205 (3) :349-358
13. Boring CC, Squires TS, Tong T, et al. Cancer statistics. CA Cancer J Clin 1994;44:7-26
14. Takeichi M. Cadherins in cancer: implications for invasion and metastasis[ J ]. CurrOpin Cell Biol .1993; 5:806-811
15. Perl AK, Wilgenbus P, Dahl U, et al. A causal role for E-cadherin in for the transition from adenoma to carcinoma[ J ]. Nature .1993;392:190-193
16. Guilford P,Hopkins J, Harraway J,McLeod M, et al. E-cadherin gremlin mutateons in familial gastric cancer.Nature 1993;392:402-405
17.Kyong,Ah Yoon, Ja-Lok Ku,et al. Germline mutateons of E-cadherin gene in Korean familial gastric cancer patients[ J ]. J Hum Genet.1999;44:177-180
18. Samuel Ko, Kent-Man Chu, John M.Luk, et al. Overexpression of LI-cadherin in gastric cancer is associated with lymph node metasis[ J ]. Biochemical and Biophysical Research Communications. 2004;319:562-568
19. Grotzinger C,Kneifel J,Patschan D, et al. LI-cadherin :a marker of gastric metaplasia and neoplasmia[ J ]. Gut 2001;49:73-81
20. Reiko Ito,Naohide Oue,Kazuhiro Yoshida, et al. Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer[J].Virchows Arch 2005:1-6
21. Chan AO, Lam SK, Chu KM, et al. Soluble E-cadherin is a valid prognostic marker in gastric carcinoma[ J ]. Gut 2001; 48:808-811
22. Chan AO, Chu KM, Lam SK, et al. Soluble E-cadherin is an independent prêtherapeutic factor for long-term survival in gastric cancer[ J ]. J Clin Oncol 2003;21:2288-2293
23 . McGinnis W,Krumlauf R. Homebox genes and axial patterning[ J ].Cell 1992;68:283-302
24. Hinoi T, Lucas PC, Kuick R, et al.CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithetium and intestinal metaplasia[ J ]. Gastroenterology 2002;123:1565-1577
25.Samuel Ko,Kent-Man Chu,John Moon-ching Luk, et al. CDX2 co-localizes with liver-intestine cadherin in intestinel metaplasia and adenocarcinoma of the stomach[ J ].Journal of Pathology. 2005;205:615-622