• 1.西安交通大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院肝膽外科(陜西西安710061);;
  • 2.新疆石河子大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院胃腸外科(新疆石河子 832002);;
  • 3.新疆石河子大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院病理科(新疆石河子832002);;
  • 4.西安交通大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院腫瘤科(陜西西安710061);

目的通過研究胃腫瘤及良性病變中尾相關(guān)同源異型盒轉(zhuǎn)錄因子-2(caudal type homeobox transcription factor-2,CDX-2)與肝腸鈣黏蛋白(LI-cadherin)的表達(dá)，探討兩者在胃癌發(fā)生、發(fā)展過程中的可能作用。方法采用免疫組織化學(xué)方法分別檢測28例正常胃黏膜、30例慢性淺表性胃炎、42例慢性萎縮性胃炎、58例腸化生胃黏膜、46例胃腺癌、30例癌旁組織以及10例胃間質(zhì)瘤組織中CDX-2和LI-cadherin蛋白的表達(dá)，并結(jié)合臨床病理特征進(jìn)行分析。結(jié)果①CDX-2與LI-cadherin蛋白在正常胃黏膜、慢性淺表性胃炎、癌旁組織以及胃間質(zhì)瘤組織中均不表達(dá); 在腸化生組織中表達(dá)陽性率分別為91.4%(53/58)和82.8%(48/58); 在胃腺癌組織中表達(dá)陽性率分別為80.4%(37/46)和65.2%(30/46)，其中腸型胃腺癌中CDX-2和LI-cadherin蛋白表達(dá)陽性率(90.6%，29/32; 78.1%,25/32)明顯高于彌漫型胃腺癌(57.1%,8/14; 35.7%,5/14)，P lt;0.05。②CDX2蛋白表達(dá)與Lauren分型(P=0.015)和腫瘤分化程度(P=0.007)有關(guān)，而LI-cadherin蛋白表達(dá)與Lauren分型(P=0.008)、淋巴結(jié)轉(zhuǎn)移(P=0.007)及臨床分期(P=0.013)有關(guān)。③在腸化生胃黏膜中，細(xì)胞核中CDX-2蛋白與細(xì)胞膜或細(xì)胞漿中LI-cadherin蛋白共同表達(dá)陽性率為83.0%(44/53)，在胃癌組織中CDX-2與LI-cadherin蛋白共同表達(dá)陽性率為67.6%(25/37)。盡管兩者表現(xiàn)出很強(qiáng)的伴隨關(guān)系，但相關(guān)性分析卻表明兩者并無相關(guān)性(r=238，P=0.115)。結(jié)論CDX2和LI-cadherin蛋白的異常表達(dá)可能分別與腸化生及胃腺癌的發(fā)生和發(fā)展有關(guān)，兩者是否具有協(xié)同作用還需進(jìn)一步研究。

引用本文： 劉仕琪,牛建華,呂毅,木拉提,王毅訓(xùn),辛國宏. CDX-2和LI-cadherin蛋白在胃腫瘤及良性病變中的表達(dá)與意義. 中國普外基礎(chǔ)與臨床雜志, 2011, 18(9): 936-941. doi: 復(fù)制

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. 吳肇漢, 吳在德. 外科學(xué) [M].第8版. 北京: 人民衛(wèi)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. 鄭見寶， 孫學(xué)軍， 王煒， 等． HIF1α與CDX2在結(jié)直腸腺癌組織中的表達(dá)及意義 [J]． 中國普外基礎(chǔ)與臨床雜志， 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. 1. Tahara E. Genetic pathways of two types of gastric cancer [J]. IARC Sci Publ, 2004(157): 327349.
  2. 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. 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. 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. 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. 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. 7. 吳肇漢, 吳在德. 外科學(xué) [M].第8版. 北京: 人民衛(wèi)生出版社, 2008: 438.
  8. 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. 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. 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. 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. 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. 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. 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. 15. 鄭見寶， 孫學(xué)軍， 王煒， 等． HIF1α與CDX2在結(jié)直腸腺癌組織中的表達(dá)及意義 [J]． 中國普外基礎(chǔ)與臨床雜志， 2010， 17(12)： 12651269．.
  16. 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. 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. 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. 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. 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. 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. 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.