MUC1、MUC3、MUC6在Barrett食管、食管腺癌、贲门肠化和贲门癌中的表达及意义
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摘要
目的:通过对人Barrett食管(BE)、食管腺癌(EA)、贲门肠化(CIM)及贲门癌(CA)标本进行MUC1、MUC3、MUC6的检测,揭示上述三种因子在BE、EA、CIM和CA发生发展中的作用,以及在BE与CIM、EA与CA鉴别中的意义。
方法:经胃镜、病理确诊的BE患者50例、CIM50例,分别取其粘膜作为BE组和CIM组,取胃镜活检或手术切除经病理确诊的EA标本25例,CA标本50例,分别作为EA组和CA组。分别取正常食管鳞状上皮20例、正常贲门粘膜20例作为正常对照组。进行免疫组化染色观察各组标本中MUC1、MUC3、MUC6蛋白的表达情况,并进行组间比较。
结果:①BE组MUC1的表达高于正常食管鳞状上皮组(P<0.01),而低于EA组(P<0.01);BE组MUC3、MUC6表达高于正常食管鳞状上皮组(P<0.01),且高于EA组(P<0.01)。②CIM组MUC1的表达低于CA组(p<0.01);CIM组MUC3的表达高于正常贲门粘膜上皮组(P<0.01),高于CA组(P<0.01);CIM组MUC6的表达低于正常贲门粘膜上皮组(P<0.01),低于CA组(P<0.01)。③MUC1、MUC6在BE和CIM、EA和CA两组疾病中的表达,差别具有统计学意义(P<0.05),而MUC3在上述两组疾病中的表达无差别(P>0.05)。④MUC1蛋白的表达与EA细胞分化程度呈负相关(P<0.05),与EA病理学分期呈正相关(P<0.05),与CA的淋巴结转移、病理学分期呈正相关(P<0.05);MUC3蛋白的表达与EA、CA细胞分化程度呈负相关(P<0.05);MUC6蛋白的表达与EA、CA的临床病理因素无关(P>0.05)。
结论:MUC1、MUC3、MUC6的表达变化与BE、EA、CIM和CA的发展呈正相关;MUC1的表达与EA细胞分化程度、病理学分期相关,与CA的淋巴结转移、病理学分期相关,MUC3的表达与EA、CA细胞分化程度呈负相关。MUC1、MUC6在BE和CIM、EA和CA中的表达不同(P<0.05),通过免疫组化方法检测MUC1、MUC6的表达水平可能成为鉴别BE和CIM、EA和CA的一条新途径。
Background and Objective: The incidence of esophageal adenocarcinoma(EA) and cardia adenocarcinoma(CA) arises greatly over the last 3 decades. Barrett’s esophagus(BE) and cardia intestinal metaplasia(CIM) are respectively the pathological changes before the cancer of EA and CA. MUC1,MUC3 and MUC6 are some of the important tumor marks.The aim of this study is to discover the role of MUC1, MUC3 and MUC6 in the pathogenesis of BE, EA, CIM and CA.
Methods: The expressions of protein of MUC1, MUC3 and MUC6 were investigated in normal esophageal squamous epithelium(n=20),normal cardia epithelium(n=20), BE(n=50), CIM(n=50), EA(n=25) and CA(n=50) using immunohistochemical staining respectively. The differences among the groups were compared.
Results:①The protein expression of MUC1 was little in normal esophageal squamous epithelium, it was more in BE and the most in EA.There was a statistically difference in MUC1 expression(P<0.01) among these three groups. The protein expression level of MUC3 and MUC6 was lower in normal esophageal squamous epithelium than that in BE(P<0.01), but higher in EA(P<0.01).②An increasing intendency of the level of MUC1 expression was observed from normal cardia epithelium to CIM and CA. There was a statistically difference in MUC1 expression(P<0.01) between CIM and CA. The expression of MUC3 was more in CIM than that in normal cardia epithelium(P<0.01),but the expression of MUC6 was less(P<0.01).③There was a statistically difference in MUC1 and MUC6 expressions(P<0.05) between BE and CIM, and between EA and CA. But no difference in MUC3 expression(P>0.05).④There was significant correlation between the expression of MUC1 and cell difference of CA or lymphatic spread or pathologic stage in CA or in EA(P<0.05). There was also correlation between the expression of MUC3 and cell difference of EA or CA (P<0.05), but no correlation between the expression of MUC6 and all the factors of clinic or pathology(P>0.05).
Conclusions: There may be close relation between the expressions of MUC1, MUC3 or MUC6 and the development from BE to EA or from CIM to CA. There is correlation between the expression of MUC1 and MUC6 and some factors of clinic or pathology of EA and CA.Monitoring these targets may provide valuable information to the diagnosis, treatment and prognosis of EA or CA. It may be a new way to distinguish BE from CIM or EA from CA by detecting the expressions of MUC1 and MUC6.
方法:经胃镜、病理确诊的BE患者50例、CIM50例,分别取其粘膜作为BE组和CIM组,取胃镜活检或手术切除经病理确诊的EA标本25例,CA标本50例,分别作为EA组和CA组。分别取正常食管鳞状上皮20例、正常贲门粘膜20例作为正常对照组。进行免疫组化染色观察各组标本中MUC1、MUC3、MUC6蛋白的表达情况,并进行组间比较。
结果:①BE组MUC1的表达高于正常食管鳞状上皮组(P<0.01),而低于EA组(P<0.01);BE组MUC3、MUC6表达高于正常食管鳞状上皮组(P<0.01),且高于EA组(P<0.01)。②CIM组MUC1的表达低于CA组(p<0.01);CIM组MUC3的表达高于正常贲门粘膜上皮组(P<0.01),高于CA组(P<0.01);CIM组MUC6的表达低于正常贲门粘膜上皮组(P<0.01),低于CA组(P<0.01)。③MUC1、MUC6在BE和CIM、EA和CA两组疾病中的表达,差别具有统计学意义(P<0.05),而MUC3在上述两组疾病中的表达无差别(P>0.05)。④MUC1蛋白的表达与EA细胞分化程度呈负相关(P<0.05),与EA病理学分期呈正相关(P<0.05),与CA的淋巴结转移、病理学分期呈正相关(P<0.05);MUC3蛋白的表达与EA、CA细胞分化程度呈负相关(P<0.05);MUC6蛋白的表达与EA、CA的临床病理因素无关(P>0.05)。
结论:MUC1、MUC3、MUC6的表达变化与BE、EA、CIM和CA的发展呈正相关;MUC1的表达与EA细胞分化程度、病理学分期相关,与CA的淋巴结转移、病理学分期相关,MUC3的表达与EA、CA细胞分化程度呈负相关。MUC1、MUC6在BE和CIM、EA和CA中的表达不同(P<0.05),通过免疫组化方法检测MUC1、MUC6的表达水平可能成为鉴别BE和CIM、EA和CA的一条新途径。
Background and Objective: The incidence of esophageal adenocarcinoma(EA) and cardia adenocarcinoma(CA) arises greatly over the last 3 decades. Barrett’s esophagus(BE) and cardia intestinal metaplasia(CIM) are respectively the pathological changes before the cancer of EA and CA. MUC1,MUC3 and MUC6 are some of the important tumor marks.The aim of this study is to discover the role of MUC1, MUC3 and MUC6 in the pathogenesis of BE, EA, CIM and CA.
Methods: The expressions of protein of MUC1, MUC3 and MUC6 were investigated in normal esophageal squamous epithelium(n=20),normal cardia epithelium(n=20), BE(n=50), CIM(n=50), EA(n=25) and CA(n=50) using immunohistochemical staining respectively. The differences among the groups were compared.
Results:①The protein expression of MUC1 was little in normal esophageal squamous epithelium, it was more in BE and the most in EA.There was a statistically difference in MUC1 expression(P<0.01) among these three groups. The protein expression level of MUC3 and MUC6 was lower in normal esophageal squamous epithelium than that in BE(P<0.01), but higher in EA(P<0.01).②An increasing intendency of the level of MUC1 expression was observed from normal cardia epithelium to CIM and CA. There was a statistically difference in MUC1 expression(P<0.01) between CIM and CA. The expression of MUC3 was more in CIM than that in normal cardia epithelium(P<0.01),but the expression of MUC6 was less(P<0.01).③There was a statistically difference in MUC1 and MUC6 expressions(P<0.05) between BE and CIM, and between EA and CA. But no difference in MUC3 expression(P>0.05).④There was significant correlation between the expression of MUC1 and cell difference of CA or lymphatic spread or pathologic stage in CA or in EA(P<0.05). There was also correlation between the expression of MUC3 and cell difference of EA or CA (P<0.05), but no correlation between the expression of MUC6 and all the factors of clinic or pathology(P>0.05).
Conclusions: There may be close relation between the expressions of MUC1, MUC3 or MUC6 and the development from BE to EA or from CIM to CA. There is correlation between the expression of MUC1 and MUC6 and some factors of clinic or pathology of EA and CA.Monitoring these targets may provide valuable information to the diagnosis, treatment and prognosis of EA or CA. It may be a new way to distinguish BE from CIM or EA from CA by detecting the expressions of MUC1 and MUC6.
引文
1.De Manzoni G, Morgagni P, Roviello F, et al. Nodal abdominal spread in adenocarcinoma of the cardia.Results of a multicenter prospective study[J]. Gastric Cancer, 1998;1(2):146.
2.O’Connor JB, Falk GW, Richter JE. The incidence of adenocarcinoma and dysplasia in Barrett’s esophagus:report on the Cleveland Clinic Barrett’s Esophagus Registry[J]. Am J Gastroenterol, 1999;9(4): 2037.
3.韩少良译. 粘蛋白[J]. 日本医学介绍, 2005;26(2):57.
4.潘国宗,许国铭,郭慧平,等. 北京上海胃食管反流症状的流行病学调查[J]. 中华消化杂志, 1999;19(4):223.
5.Falk GW, Richter JE. Reflux disease and Barrett's esophagus[J]. Endoscopy, 1998; 30(2): 61.
6.Kraan MC, Smith MD, Weedon H, et al. Measurement of cytokine and adhesion molecule expression in synovial tissue by digital image analysis[J]. Ann Rheum Dis, 2001; 60(3):296.
7.Spechler SJ, Robbins AH, Robbins HB, et al. Adenocarcinoma and Barrett’s esophagus[J]. Anoverrated Risk Gastroenterology, 1998;87(6): 927.
8. Pera M, Cameron AJ, Trastek VF, et al. Gastroenterology[J]. 1993 ;104(2): 510.
9.王雯,张志坚,林克荣,等. 福建地区 BE 的发病情况和内镜及临床特点[J].中华内科杂志, 2006;45(5): 393.
10.许军英,张锦坤.反流性食管炎患者食管酸反流类型的探讨[J].中华消化杂志, 1997;17(5): 265.
11.Eisen GM, Sandier RS. Murray S, et al[J]. Am J Gastroenterol, 1997; 92(1): 27.
12.Jenkins GJ, Doak SH, Parry JM, et al. Genetic pathways involved in the progression of Barrett’s metaplasia to adenocarcinoma[J]. Br J Surg, 2002;89(7): 824.
13.Arul GS, Moorghen M, Myerscough N, et al. Mucin gene expression in Barrett’s esophagus: an in situ hybridization and immunohistochemical study[J]. Gut, 2000; 47 (6): 753.
14.张海生,鲁海文,孔广忠,等 MUC1在胰腺肿瘤中的表达及意义[J]. 现代肿瘤学,2005;13(6): 756.
15. Dong Y. Walsh MD. Cummings MC, et a1.Expression of MUC1 and MUC2 inepithelial ovarian tumours[J]. Patho1,1997; 183(3): 311.
16.Gum JR, Hicks Jw, Swallow DM, et al.Molecular cloning of cDNAs of derived from a novel human intestinal mucin gene[J]. Biochem Biophys Res Commun, 1990; 171(1): 407.
17.Reid CJ, Harris A. Developmental expression of mucin genes in the human gastrointestinal system[J]. Gut , 1998; 42(2): 220.
18. Glickman JN, Shahsafaei A, Odze RD. Mucin Core Peptide Expression Can Help Differentiate Barrett’s Esophagus From Intestinal Metaplasia of the Stomach[J]. Am J Surg Pathol, 2003; 27(10): 1357.
19.Toribara N W, Roberton AM, Ho SB , et al. Human gastric mucin: identification of a unique species by expression cloning[J]. Biol Chem, 1993; 268(8): 5879.
20. Samuel SB, Shekel LL, Toribara NW, et al. Mucin gene expression in normal, preneoplastic and neoplastic human gastric epithelium[J]. Cancer Res, 1995; 55(15): 2681.
21.汪荣泉, 房殿春, 刘为纹,等. 胃癌及癌前病变组织中MUC6核粘蛋白的表达及其意义[J]. 第三军医大学学报, 2001;23(1):9.
22.Morales TG, Sampliner RE, Bhattacharyya A. Intestinal metaplasia of the cardia[J]. Am J Gastroenterol, 1997; 92(3):414.
23.Pereira AD, Suspiro A, Chaves P, et al. Short segments of Barrett’s epithelium and intestinal metaplasia in normal appearing oesophagogastric junctions: the same or two different entities? [J]. Gut, 1998; 42(5):659.
24.庄则豪, 王立东, 高珊珊,等. 河南食管癌高发区食管和CA组织中粘蛋白1 的表达[J].郑州大学学报(医学版), 2002; 37(6): 774.
25.周琦, 白永敏, 王立东, 等. CA高、低发区居民责门癌前病变和癌组织中MUC3蛋白表达的比较[J]. 郑州大学学报(医学版),2003; 38(3):324.
26.Reid BJ, Blount: PL, Rubin CE, et a1. Flow-cytometric and histological progression tomalignancy in Barrett’s esophagus: prospective endoscopic surveillance of a cohort[J]. Gastroenterology, 1992; 102(4): 1212.
27.Paull G, Yardley JH. Gastric and esophageal Campylobacter pylori in pylori in patients with Barrett’s esophagus[J]. Gastroenterology, 1988; 95(1): 216.
28.Abbas Z, Hussainy AS, Ibrahim F, et al.Barrett’s oesophagus and Helicobacterpylori[J]. Gastroenterol Hepatol, 1995;10(3): 331.
29.Kogan Z, Corti R, Cabane A, et al. Helicobacter pylori in Barrett esophagus[J]. Acta Gastroenterol Latinoam, 1992; 22(4): 215.
30.Gulmann C, Shaqaqi OA, Grace A, et al. Cytokeratin 7/20 and MUC1, 2, 5AC, and 6 expression patterns in Barrett's esophagus and intestinal metaplasia of the stomach: intestinal metaplasia of the cardia is related to Barrett's esophagus[J]. Appl-Immunohistochem-Mol-Morphol,2004; 12(2): 142.
1.张天泽,徐光炜. 肿瘤学(第 1 版)[M].天津科学技术出版社,1998;1265.
2.Wittekind C,Henson DE, Hutter RVP, et al. TNM Supplement. A Commentary on Uniform Use 2nd ed[J]. New York Wiley-Liss, 2001;93(3):222.
3.De Manzoni G, Morgagni P, Roviello F, et al. Nodal abdominal spread in adenocarcinoma of the cardia.Results of a multicenter prospective study[J]. Gastric Cancer ,1998;1(2):146.
4.Siewert JR, Feith M, Werner M, et al .Adenocarcinoma of the esophagogastric junction. Results of surgical therapy based on anatomical/topographic classification in1002 consecutive patients[J], Ann Surg,2000;232(2):353.
5.Feith M , Stein HJ, Siewert JR, et al. Pattern of lymphatic spread of Barrett’s cancer[J]. World J Surg ,2003;27(9):1052.
6. 许 桦 林 . 幽 门 螺 旋 杆 菌 与 胃 食 管 反 流 病 的 关 系 [J]. 医 学 新 知 杂志,2004;14(4):221.
7.Beuzen F,Dubois S,Flejou JF, et al.Chromosomal numerical aberrations are frequent in oesophageal and gastric adenocarcinomas:a study using in-situ hybridization[J]. Histopathology,2000;37(3):241.
8.Tselepis Chris,Perry Ian,Dawson Chris, et al [J]. Oncogene,2002;21(39):6071.
9.赵丽珍,郑可,张军.贲门癌的发病机制研究现状[J].国外医学.消化系统疾病分册,2003;23(4):231.
10.Spechler SJ, Robbins AH, Robbins HB, et al. Adenocarcinoma and Brarrett’s esophagus[J]. An overrated irsk Gastroenterology,1984; 87(4):927.
11.Ransford RA,Jankowski JA. Genetic versus environmental interactions in the oesphagitis-metaplasia-dysplasia-adenocarcinoma sequence(MCS) of Barrett’s esophagus[J]. Acta Gastrocnterol Belg,2000; 63(1):18.
12. Van Lier MG, Bomhof FJ, Leendertse I, et al, Cytokeratin phenotyping does not help in distinguishing oesophageal adenocarcinoma from cancer of the gastric cardia[J]. Clin Pathol, 2005;58(7):722.
13.Farrow DC, Voughan TL, Hansten PD, et al. Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer[J]. Cancer Epidemicl Biomarkers P rev, 1998;7(2):97.
14.Balaji NS, DeMeesier SR, Wickramasinghe KS, et al. Etiology of intestinal metaplasia at the gastroesophageal junction[J]. Surg Endosc, 2003; 17(1): 43.
15.Van Sandick JW, Van Lanschot JB, Van Felius L,et al. Intestinal metaplasia of the esophagus or esophagogastric junction:evidence of distict clinical,pathologic and histochemical staining features[J]. Am J Clin Pathol, 2002;117(1):117.
16.Van Lier MG,Bomhof FJ, Leendertse I, et al. Cytokeratin phenotyping does not help in distinguishing oesophageal adenocarcinoma from cancer of the gastric cardia[J]. Clin Pathol, 2005;58(7):722.
17.Souza RF, Shew make K, Beer DG, et al. Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenoearcinoma cells[J]. Cancer Res, 2000;60(20):5767.
18. Buskens CJ, SivulaA, van Rees BP, et al. Comparison of cyclooxygenase 2 expression in adenocarcinomas of the gastric cardia and distal oesophagus[J]. Gastric Cancer,2003;52(12):1678.
19.蓝斌,李木泉,沈金辉. P53 蛋白与增殖细胞核抗原在食管、贲门癌中的表达及临床意义[J].中国胸外科临床杂志,2000;7(1):71
20.Van Dekken H, Geelen E, Dinjens WN, et al. Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of discrimination between esophageal(Barrett’s)and gastric cardia adenocarcinomas[J]. Cancer RES ,1999;59(3):748.
21.Yanagi M, Keller G, Mucller J, et al. Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach[J]. Virchows Arch, 2000;,437(6):605.
22.Lin JT, Wu MS ,Shun CT, et al. Microsatellite instability in gastric carcinoma with special references to histopathology and cancer stages[J]. Eur J Cancer, 1995; 31A(11):1879.
23.Driessen A, Van Raemdonck D, De Leyn P. et al.Are carcinomas of the cardiaoesophageal or gastric adenocarcinomas?[J]. European Journal of Cancer, 2003;39(12):2487.
24.Sampliner RE. The Practie Parameters Committee of the Amarican College of Gastroenterology. Update guidelines for the diagnosis,surveillance and therpy of barrett,esophagus[J]. Am J Gastroenterol,2002;97(2):1888.
25.Fennerty MB. Gastric intestinal metaplasia on routine endoscopic biopsy[J]. Gastroeuterology, 2003;125(2):586.
26.EL-Zimaity HM. Graham DY. Cytokeratin subsets for distinguishing endoscopic biopsy specimeus[J]. Am J Gastroenterol,2001;96(5):1378.
27.Morales CP. Spechler SJ. Intestinal metoplasia at the gastroesophageal junction: Barrett,s,Bacteria, and Biomarkers[J]. Am J Gastroenterol, 2003,98(4):759.
2.O’Connor JB, Falk GW, Richter JE. The incidence of adenocarcinoma and dysplasia in Barrett’s esophagus:report on the Cleveland Clinic Barrett’s Esophagus Registry[J]. Am J Gastroenterol, 1999;9(4): 2037.
3.韩少良译. 粘蛋白[J]. 日本医学介绍, 2005;26(2):57.
4.潘国宗,许国铭,郭慧平,等. 北京上海胃食管反流症状的流行病学调查[J]. 中华消化杂志, 1999;19(4):223.
5.Falk GW, Richter JE. Reflux disease and Barrett's esophagus[J]. Endoscopy, 1998; 30(2): 61.
6.Kraan MC, Smith MD, Weedon H, et al. Measurement of cytokine and adhesion molecule expression in synovial tissue by digital image analysis[J]. Ann Rheum Dis, 2001; 60(3):296.
7.Spechler SJ, Robbins AH, Robbins HB, et al. Adenocarcinoma and Barrett’s esophagus[J]. Anoverrated Risk Gastroenterology, 1998;87(6): 927.
8. Pera M, Cameron AJ, Trastek VF, et al. Gastroenterology[J]. 1993 ;104(2): 510.
9.王雯,张志坚,林克荣,等. 福建地区 BE 的发病情况和内镜及临床特点[J].中华内科杂志, 2006;45(5): 393.
10.许军英,张锦坤.反流性食管炎患者食管酸反流类型的探讨[J].中华消化杂志, 1997;17(5): 265.
11.Eisen GM, Sandier RS. Murray S, et al[J]. Am J Gastroenterol, 1997; 92(1): 27.
12.Jenkins GJ, Doak SH, Parry JM, et al. Genetic pathways involved in the progression of Barrett’s metaplasia to adenocarcinoma[J]. Br J Surg, 2002;89(7): 824.
13.Arul GS, Moorghen M, Myerscough N, et al. Mucin gene expression in Barrett’s esophagus: an in situ hybridization and immunohistochemical study[J]. Gut, 2000; 47 (6): 753.
14.张海生,鲁海文,孔广忠,等 MUC1在胰腺肿瘤中的表达及意义[J]. 现代肿瘤学,2005;13(6): 756.
15. Dong Y. Walsh MD. Cummings MC, et a1.Expression of MUC1 and MUC2 inepithelial ovarian tumours[J]. Patho1,1997; 183(3): 311.
16.Gum JR, Hicks Jw, Swallow DM, et al.Molecular cloning of cDNAs of derived from a novel human intestinal mucin gene[J]. Biochem Biophys Res Commun, 1990; 171(1): 407.
17.Reid CJ, Harris A. Developmental expression of mucin genes in the human gastrointestinal system[J]. Gut , 1998; 42(2): 220.
18. Glickman JN, Shahsafaei A, Odze RD. Mucin Core Peptide Expression Can Help Differentiate Barrett’s Esophagus From Intestinal Metaplasia of the Stomach[J]. Am J Surg Pathol, 2003; 27(10): 1357.
19.Toribara N W, Roberton AM, Ho SB , et al. Human gastric mucin: identification of a unique species by expression cloning[J]. Biol Chem, 1993; 268(8): 5879.
20. Samuel SB, Shekel LL, Toribara NW, et al. Mucin gene expression in normal, preneoplastic and neoplastic human gastric epithelium[J]. Cancer Res, 1995; 55(15): 2681.
21.汪荣泉, 房殿春, 刘为纹,等. 胃癌及癌前病变组织中MUC6核粘蛋白的表达及其意义[J]. 第三军医大学学报, 2001;23(1):9.
22.Morales TG, Sampliner RE, Bhattacharyya A. Intestinal metaplasia of the cardia[J]. Am J Gastroenterol, 1997; 92(3):414.
23.Pereira AD, Suspiro A, Chaves P, et al. Short segments of Barrett’s epithelium and intestinal metaplasia in normal appearing oesophagogastric junctions: the same or two different entities? [J]. Gut, 1998; 42(5):659.
24.庄则豪, 王立东, 高珊珊,等. 河南食管癌高发区食管和CA组织中粘蛋白1 的表达[J].郑州大学学报(医学版), 2002; 37(6): 774.
25.周琦, 白永敏, 王立东, 等. CA高、低发区居民责门癌前病变和癌组织中MUC3蛋白表达的比较[J]. 郑州大学学报(医学版),2003; 38(3):324.
26.Reid BJ, Blount: PL, Rubin CE, et a1. Flow-cytometric and histological progression tomalignancy in Barrett’s esophagus: prospective endoscopic surveillance of a cohort[J]. Gastroenterology, 1992; 102(4): 1212.
27.Paull G, Yardley JH. Gastric and esophageal Campylobacter pylori in pylori in patients with Barrett’s esophagus[J]. Gastroenterology, 1988; 95(1): 216.
28.Abbas Z, Hussainy AS, Ibrahim F, et al.Barrett’s oesophagus and Helicobacterpylori[J]. Gastroenterol Hepatol, 1995;10(3): 331.
29.Kogan Z, Corti R, Cabane A, et al. Helicobacter pylori in Barrett esophagus[J]. Acta Gastroenterol Latinoam, 1992; 22(4): 215.
30.Gulmann C, Shaqaqi OA, Grace A, et al. Cytokeratin 7/20 and MUC1, 2, 5AC, and 6 expression patterns in Barrett's esophagus and intestinal metaplasia of the stomach: intestinal metaplasia of the cardia is related to Barrett's esophagus[J]. Appl-Immunohistochem-Mol-Morphol,2004; 12(2): 142.
1.张天泽,徐光炜. 肿瘤学(第 1 版)[M].天津科学技术出版社,1998;1265.
2.Wittekind C,Henson DE, Hutter RVP, et al. TNM Supplement. A Commentary on Uniform Use 2nd ed[J]. New York Wiley-Liss, 2001;93(3):222.
3.De Manzoni G, Morgagni P, Roviello F, et al. Nodal abdominal spread in adenocarcinoma of the cardia.Results of a multicenter prospective study[J]. Gastric Cancer ,1998;1(2):146.
4.Siewert JR, Feith M, Werner M, et al .Adenocarcinoma of the esophagogastric junction. Results of surgical therapy based on anatomical/topographic classification in1002 consecutive patients[J], Ann Surg,2000;232(2):353.
5.Feith M , Stein HJ, Siewert JR, et al. Pattern of lymphatic spread of Barrett’s cancer[J]. World J Surg ,2003;27(9):1052.
6. 许 桦 林 . 幽 门 螺 旋 杆 菌 与 胃 食 管 反 流 病 的 关 系 [J]. 医 学 新 知 杂志,2004;14(4):221.
7.Beuzen F,Dubois S,Flejou JF, et al.Chromosomal numerical aberrations are frequent in oesophageal and gastric adenocarcinomas:a study using in-situ hybridization[J]. Histopathology,2000;37(3):241.
8.Tselepis Chris,Perry Ian,Dawson Chris, et al [J]. Oncogene,2002;21(39):6071.
9.赵丽珍,郑可,张军.贲门癌的发病机制研究现状[J].国外医学.消化系统疾病分册,2003;23(4):231.
10.Spechler SJ, Robbins AH, Robbins HB, et al. Adenocarcinoma and Brarrett’s esophagus[J]. An overrated irsk Gastroenterology,1984; 87(4):927.
11.Ransford RA,Jankowski JA. Genetic versus environmental interactions in the oesphagitis-metaplasia-dysplasia-adenocarcinoma sequence(MCS) of Barrett’s esophagus[J]. Acta Gastrocnterol Belg,2000; 63(1):18.
12. Van Lier MG, Bomhof FJ, Leendertse I, et al, Cytokeratin phenotyping does not help in distinguishing oesophageal adenocarcinoma from cancer of the gastric cardia[J]. Clin Pathol, 2005;58(7):722.
13.Farrow DC, Voughan TL, Hansten PD, et al. Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer[J]. Cancer Epidemicl Biomarkers P rev, 1998;7(2):97.
14.Balaji NS, DeMeesier SR, Wickramasinghe KS, et al. Etiology of intestinal metaplasia at the gastroesophageal junction[J]. Surg Endosc, 2003; 17(1): 43.
15.Van Sandick JW, Van Lanschot JB, Van Felius L,et al. Intestinal metaplasia of the esophagus or esophagogastric junction:evidence of distict clinical,pathologic and histochemical staining features[J]. Am J Clin Pathol, 2002;117(1):117.
16.Van Lier MG,Bomhof FJ, Leendertse I, et al. Cytokeratin phenotyping does not help in distinguishing oesophageal adenocarcinoma from cancer of the gastric cardia[J]. Clin Pathol, 2005;58(7):722.
17.Souza RF, Shew make K, Beer DG, et al. Selective inhibition of cyclooxygenase-2 suppresses growth and induces apoptosis in human esophageal adenoearcinoma cells[J]. Cancer Res, 2000;60(20):5767.
18. Buskens CJ, SivulaA, van Rees BP, et al. Comparison of cyclooxygenase 2 expression in adenocarcinomas of the gastric cardia and distal oesophagus[J]. Gastric Cancer,2003;52(12):1678.
19.蓝斌,李木泉,沈金辉. P53 蛋白与增殖细胞核抗原在食管、贲门癌中的表达及临床意义[J].中国胸外科临床杂志,2000;7(1):71
20.Van Dekken H, Geelen E, Dinjens WN, et al. Comparative genomic hybridization of cancer of the gastroesophageal junction: deletion of discrimination between esophageal(Barrett’s)and gastric cardia adenocarcinomas[J]. Cancer RES ,1999;59(3):748.
21.Yanagi M, Keller G, Mucller J, et al. Comparison of loss of heterozygosity and microsatellite instability in adenocarcinomas of the distal esophagus and proximal stomach[J]. Virchows Arch, 2000;,437(6):605.
22.Lin JT, Wu MS ,Shun CT, et al. Microsatellite instability in gastric carcinoma with special references to histopathology and cancer stages[J]. Eur J Cancer, 1995; 31A(11):1879.
23.Driessen A, Van Raemdonck D, De Leyn P. et al.Are carcinomas of the cardiaoesophageal or gastric adenocarcinomas?[J]. European Journal of Cancer, 2003;39(12):2487.
24.Sampliner RE. The Practie Parameters Committee of the Amarican College of Gastroenterology. Update guidelines for the diagnosis,surveillance and therpy of barrett,esophagus[J]. Am J Gastroenterol,2002;97(2):1888.
25.Fennerty MB. Gastric intestinal metaplasia on routine endoscopic biopsy[J]. Gastroeuterology, 2003;125(2):586.
26.EL-Zimaity HM. Graham DY. Cytokeratin subsets for distinguishing endoscopic biopsy specimeus[J]. Am J Gastroenterol,2001;96(5):1378.
27.Morales CP. Spechler SJ. Intestinal metoplasia at the gastroesophageal junction: Barrett,s,Bacteria, and Biomarkers[J]. Am J Gastroenterol, 2003,98(4):759.