Ki67、CDX2在C型、D型和E型腺管开口肠上皮化生胃黏膜组织中的差异表达
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摘要
目的:检测C型、D型和E型腺管开口肠上皮化生胃黏膜组织中Ki67、CDX2的表达情况,评估肠上皮化生程度(intestinal metaplasia,IM)与腺管开口形态的相关性.方法:应用免疫组织化学EnVision二步法检测Ki67、CDX2蛋白在452例不同腺管开口胃黏膜病变中的表达情况;苏木素-伊红染色法评估IM的程度.结果:在非萎缩性胃炎胃小凹腺管开口呈B型(B型腺管开口胃炎)、萎缩性胃炎伴IM胃小凹腺管开口呈C型(C型腺管IM)、萎缩性胃炎伴IM胃小凹腺管开口呈D型(D型腺管IM)、萎缩性胃炎伴IM胃小凹腺管开口呈E型(E型腺管IM)、低级别上皮内瘤变和胃窦腺癌组织中Ki67蛋白的表达阳性率分别为16.2%、40.5%、44.0%、64.3%、71.4%和87.1%,E型腺管IM组分别与C、D组之间差别有统计学意义(P=0.002,=0.008),而C与D组差异无统计学意义;以上6组中CDX2蛋白的表达阳性率分别为21.6%、75.0%、78.6%、81.0%、80.4%和84.3%,E型腺管IM组与C、D组之间没有统计学上的差异,但与B型腺管开口胃炎组的差异有统计学意义(P=0.000).IM程度E型>D型>C型,差异有统计学意义(P=0.000).结论:CDX2可能与胃黏膜IM组织的微形态无关;E型腺管IM黏膜比C型、D型的Ki67表达高,IM程度重,胃镜随访检查时应重视这些黏膜改变的活检.
AIM:To detect the expression of Ki67 and CDX2 in intestinal metaplasia(IM) among gastric mucosa appearing as type C,D or E pit pattern,and to assess the correlation between the degree of IM and the morphology of gastric pits.METHODS:Immunohistochemistry was used to examine the expression of Ki67 and CDX2 proteins in 452 cases of gastric mucosal lesions with different pit patterns.The degree of IM was evaluated by hematoxylin and eosin staining.RESULTS:The positive rates of Ki67 in nonatrophic gastritis(NAG) appearing as type B pit pattern(BG),atrophic gastritis(AG) with IM appearing as type C pit pattern(CIM),AG with IM appearing as type D pit pattern(DIM),AG with IM appearing as type E pit pattern(EIM),low intraepithelial neoplasia(LIN),and gastric antrum adenocarcinoma(GAAC) were 16.2%,40.5%,44.0%,64.3%,71.4%,and 87.1%,respectively.The positive rate of Ki67 protein in EIM was significantly different from those in CIM and DIM(P=0.002,0.008),but there was no difference between CIM and DIM.The positive rates of CDX2 protein were 21.6%,75.0%,78.6%,81.0%,80.4%,and 84.3% in the above groups,respectively.The positive rate of CDX2 protein in EIM was signif icantly different from that in BG(P=0.000),but not different from those in CIM and DIM.The degree of IM was significantly higher in EIM than in DIM and CIM(P=0.000).CONCLUSION:CDX2 may have no relationship with micromorphology of IM in gastric mucosa.The expression of Ki67 protein and the degree of IM in EIM were higher than those in CIM and DIM.
AIM:To detect the expression of Ki67 and CDX2 in intestinal metaplasia(IM) among gastric mucosa appearing as type C,D or E pit pattern,and to assess the correlation between the degree of IM and the morphology of gastric pits.METHODS:Immunohistochemistry was used to examine the expression of Ki67 and CDX2 proteins in 452 cases of gastric mucosal lesions with different pit patterns.The degree of IM was evaluated by hematoxylin and eosin staining.RESULTS:The positive rates of Ki67 in nonatrophic gastritis(NAG) appearing as type B pit pattern(BG),atrophic gastritis(AG) with IM appearing as type C pit pattern(CIM),AG with IM appearing as type D pit pattern(DIM),AG with IM appearing as type E pit pattern(EIM),low intraepithelial neoplasia(LIN),and gastric antrum adenocarcinoma(GAAC) were 16.2%,40.5%,44.0%,64.3%,71.4%,and 87.1%,respectively.The positive rate of Ki67 protein in EIM was significantly different from those in CIM and DIM(P=0.002,0.008),but there was no difference between CIM and DIM.The positive rates of CDX2 protein were 21.6%,75.0%,78.6%,81.0%,80.4%,and 84.3% in the above groups,respectively.The positive rate of CDX2 protein in EIM was signif icantly different from that in BG(P=0.000),but not different from those in CIM and DIM.The degree of IM was significantly higher in EIM than in DIM and CIM(P=0.000).CONCLUSION:CDX2 may have no relationship with micromorphology of IM in gastric mucosa.The expression of Ki67 protein and the degree of IM in EIM were higher than those in CIM and DIM.
引文
1Zhang J,Guo SB,Duan ZJ.Application of magnify-ing narrow-band imaging endoscopy for diagnosis of early gastric cancer and precancerous lesion.BMC Gastroenterol2011;11:135
2Li HY,Ge ZZ,Fujishiro M,Li XB.Current clinical applications of magnifying endoscopy with narrow band imaging in the stomach.Diagn Ther Endosc2012;2012:271914
3Nass JP,Connolly SE.Current status of chromoen-doscopy and narrow band imaging in colonoscopy.Clin Colon Rectal Surg2010;23:21-30
4Gono K,Obi T,Yamaguchi M,Ohyama N,MachidaH,Sano Y,Yoshida S,Hamamoto Y,Endo T.Ap-pearance of enhanced tissue features in narrow-band endoscopic imaging.J Biomed Opt2004;9:568-577
5Sakaki N,Iida Y,Okazaki Y,Kawamura S,Take-moto T.Magnifying endoscopic observation of the gastric mucosa,particularly in patients with atro-phic gastritis.Endoscopy1978;10:269-274
6中华医学会消化病学分会.中国慢性胃炎共识意见.中华消化内镜杂志2007;24:58-63
7Yang JM,Chen L,Fan YL,Li XH,Yu X,Fang DC.Endoscopic patterns of gastric mucosa and its clini-copathological significance.World J Gastroenterol2003;9:2552-2556
8李娜,张亚历,刘思德,姜泊,潘德寿,智发朝,陈村龙,李明松,姚永莉,陈烨,白杨,龚伟,姚国和.放大内镜下萎缩性胃炎胃窦黏膜小凹开口形态变化及其影响因素的分析.中华消化内镜杂志2008;25:201-203
9严山,凌红,徐永成.胃癌前病变黏膜微细结构形态变化与组织学改变相关性研究.临床消化病杂志2011;23:160-162
10陈磊,杨建民,李向红,余欣,房殿春.放大内镜下胃病患者胃黏膜微细结构改变及其临床病理意义.中华消化内镜杂志2003;20:83-87
11原丽莉,陈星,汪嵘,康艳,侯波.胃小凹腺管开口分型与幽门螺杆菌及慢性胃炎相关性研究.中国药物与临床2008;8:648-650
12Zhang MQ,Lin F,Hui P,Chen ZM,Ritter JH,Wang HL.Expression of mucins,SIMA,villin,and CDX2in small-intestinal adenocarcinoma.Am J Clin Pathol2007;128:808-816
13Kang JM,Lee BH,Kim N,Lee HS,Lee HE,Park JH,Kim JS,Jung HC,Song IS.CDX1and CDX2expres-sion in intestinal metaplasia,dysplasia and gastric cancer.J Korean Med Sci2011;26:647-653
14Hayes S,Ahmed S,Clark P.Immunohistochemi-cal assessment for Cdx2expression in the Barrett metaplasia-dysplasia-adenocarcinoma sequence.J Clin Pathol2011;64:110-113
15Park do Y,Srivastava A,Kim GH,Mino-Kenudson M,Deshpande V,Zukerberg LR,Song GA,Lauwers GY.CDX2expression in the intestinal-type gastric epithelial neoplasia:frequency and significance.Mod Pathol2010;23:54-61
16Qin R,Wang NN,Chu J,Wang X.Expression and signifi cance of homeodomain protein Cdx2in gas-tric carcinoma and precancerous lesions.World J Gastroenterol2012;18:3296-3302
17王旭光,张忠,孙丽萍,袁媛.同源异形盒基因CDX2的表达与胃黏膜肠上皮化生类型的关系.世界华人消化杂志2009;17:86-89
18Liu Q,Teh M,Ito K,Shah N,Ito Y,Yeoh KG.CDX2expression is progressively decreased in human gastric intestinal metaplasia,dysplasia and cancer.Mod Pathol2007;20:1286-1297
19Xiao ZY,Ru Y,Sun JT,Gao SG,Wang YF,Wang LD,Feng XS.Expression of CDX2and villin in gas-tric cardiac intestinal metaplasia and the relation with gastric cardiac carcinogenesis.Asian Pac J Can-cer Prev2012;13:247-250
20Baba Y,Nosho K,Shima K,Freed E,Irahara N,Philips J,Meyerhardt JA,Hornick JL,Shivdasani RA,Fuchs CS,Ogino S.Relationship of CDX2loss with molecular features and prognosis in colorectal cancer.Clin Cancer Res2009;15:4665-4673
21Lee BH,Kim N,Lee HS,Kang JM,Park HK,Jo HJ,Shin CM,Lee SH,Park YS,Hwang JH,Kim JW,Jeong SH,Lee DH,Jung HC,Song IS.The Role ofCDX2in Intestinal Metaplasia Evaluated Using Im-munohistochemistry.Gut Liver2012;6:71-77
22Zheng Y,Wang L,Zhang JP,Yang JY,Zhao ZM,Zhang XY.Expression of p53,c-erbB-2and Ki67in intestinal metaplasia and gastric carcinoma.World J Gastroenterol2010;16:339-344
23Duchrow M,Schlüter C,Key G,Kubbutat MH,Wohlenberg C,Flad HD,Gerdes J.Cell prolifera-tion-associated nuclear antigen def ined by antibody Ki-67:a new kind of cell cycle-maintaining proteins.Arch Immunol Ther Exp(Warsz)1995;43:117-121
24Gerdes J,Lemke H,Baisch H,Wacker HH,Schwab U,Stein H.Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.J Immunol1984;133:1710-1715
25Preusser M,Heinzl H,Gelpi E,Hftberger R,Fischer I,Pipp I,Milenkovic I,Whrer A,Popovici F,Wolfsberger S,Hainfellner JA.Ki67index in intra-cranial ependymoma:a promising histopathological candidate biomarker.Histopathology2008;53:39-47
26Igarashi N,Takahashi M,Ohkubo H,Omata K,Iida R,Fujimoto S.Predictive value of Ki-67,p53pro-tein,and DNA content in the diagnosis of gastric carcinoma.Cancer1999;86:1449-1454
27Forones NM,Carvalho AP,Giannotti-Filho O,Lou-reno LG,Oshima CT.Cell proliferation and apop-tosis in gastric cancer and intestinal metaplasia.Arq Gastroenterol2005;42:30-34
28Tut VM,Braithwaite KL,Angus B,Neal DE,Lunec J,Mellon JK.Cyclin D1expression in transitional cell carcinoma of the bladder:correlation with p53,waf1,pRb and Ki67.Br J Cancer2001;84:270-275
29郁岩杰,赵治国,于泳,任景丽,王宪远,虎建恩,弋晓萍,温静,冯常炜,李振峰,唐芙爱.萎缩性胃炎伴肠上皮化生浅表隆起灶黏膜中Reg4和Ki67表达高于浅表凹陷灶黏膜.肿瘤2011;31:937-941
30黄永辉,周丽雅,林三仁,金珠,刘建军,丁士刚,夏志伟,段丽萍,常红.放大内镜下胃小凹形态学分类及其临床病理意义.中国内镜杂志2004;10:14-16,19
2Li HY,Ge ZZ,Fujishiro M,Li XB.Current clinical applications of magnifying endoscopy with narrow band imaging in the stomach.Diagn Ther Endosc2012;2012:271914
3Nass JP,Connolly SE.Current status of chromoen-doscopy and narrow band imaging in colonoscopy.Clin Colon Rectal Surg2010;23:21-30
4Gono K,Obi T,Yamaguchi M,Ohyama N,MachidaH,Sano Y,Yoshida S,Hamamoto Y,Endo T.Ap-pearance of enhanced tissue features in narrow-band endoscopic imaging.J Biomed Opt2004;9:568-577
5Sakaki N,Iida Y,Okazaki Y,Kawamura S,Take-moto T.Magnifying endoscopic observation of the gastric mucosa,particularly in patients with atro-phic gastritis.Endoscopy1978;10:269-274
6中华医学会消化病学分会.中国慢性胃炎共识意见.中华消化内镜杂志2007;24:58-63
7Yang JM,Chen L,Fan YL,Li XH,Yu X,Fang DC.Endoscopic patterns of gastric mucosa and its clini-copathological significance.World J Gastroenterol2003;9:2552-2556
8李娜,张亚历,刘思德,姜泊,潘德寿,智发朝,陈村龙,李明松,姚永莉,陈烨,白杨,龚伟,姚国和.放大内镜下萎缩性胃炎胃窦黏膜小凹开口形态变化及其影响因素的分析.中华消化内镜杂志2008;25:201-203
9严山,凌红,徐永成.胃癌前病变黏膜微细结构形态变化与组织学改变相关性研究.临床消化病杂志2011;23:160-162
10陈磊,杨建民,李向红,余欣,房殿春.放大内镜下胃病患者胃黏膜微细结构改变及其临床病理意义.中华消化内镜杂志2003;20:83-87
11原丽莉,陈星,汪嵘,康艳,侯波.胃小凹腺管开口分型与幽门螺杆菌及慢性胃炎相关性研究.中国药物与临床2008;8:648-650
12Zhang MQ,Lin F,Hui P,Chen ZM,Ritter JH,Wang HL.Expression of mucins,SIMA,villin,and CDX2in small-intestinal adenocarcinoma.Am J Clin Pathol2007;128:808-816
13Kang JM,Lee BH,Kim N,Lee HS,Lee HE,Park JH,Kim JS,Jung HC,Song IS.CDX1and CDX2expres-sion in intestinal metaplasia,dysplasia and gastric cancer.J Korean Med Sci2011;26:647-653
14Hayes S,Ahmed S,Clark P.Immunohistochemi-cal assessment for Cdx2expression in the Barrett metaplasia-dysplasia-adenocarcinoma sequence.J Clin Pathol2011;64:110-113
15Park do Y,Srivastava A,Kim GH,Mino-Kenudson M,Deshpande V,Zukerberg LR,Song GA,Lauwers GY.CDX2expression in the intestinal-type gastric epithelial neoplasia:frequency and significance.Mod Pathol2010;23:54-61
16Qin R,Wang NN,Chu J,Wang X.Expression and signifi cance of homeodomain protein Cdx2in gas-tric carcinoma and precancerous lesions.World J Gastroenterol2012;18:3296-3302
17王旭光,张忠,孙丽萍,袁媛.同源异形盒基因CDX2的表达与胃黏膜肠上皮化生类型的关系.世界华人消化杂志2009;17:86-89
18Liu Q,Teh M,Ito K,Shah N,Ito Y,Yeoh KG.CDX2expression is progressively decreased in human gastric intestinal metaplasia,dysplasia and cancer.Mod Pathol2007;20:1286-1297
19Xiao ZY,Ru Y,Sun JT,Gao SG,Wang YF,Wang LD,Feng XS.Expression of CDX2and villin in gas-tric cardiac intestinal metaplasia and the relation with gastric cardiac carcinogenesis.Asian Pac J Can-cer Prev2012;13:247-250
20Baba Y,Nosho K,Shima K,Freed E,Irahara N,Philips J,Meyerhardt JA,Hornick JL,Shivdasani RA,Fuchs CS,Ogino S.Relationship of CDX2loss with molecular features and prognosis in colorectal cancer.Clin Cancer Res2009;15:4665-4673
21Lee BH,Kim N,Lee HS,Kang JM,Park HK,Jo HJ,Shin CM,Lee SH,Park YS,Hwang JH,Kim JW,Jeong SH,Lee DH,Jung HC,Song IS.The Role ofCDX2in Intestinal Metaplasia Evaluated Using Im-munohistochemistry.Gut Liver2012;6:71-77
22Zheng Y,Wang L,Zhang JP,Yang JY,Zhao ZM,Zhang XY.Expression of p53,c-erbB-2and Ki67in intestinal metaplasia and gastric carcinoma.World J Gastroenterol2010;16:339-344
23Duchrow M,Schlüter C,Key G,Kubbutat MH,Wohlenberg C,Flad HD,Gerdes J.Cell prolifera-tion-associated nuclear antigen def ined by antibody Ki-67:a new kind of cell cycle-maintaining proteins.Arch Immunol Ther Exp(Warsz)1995;43:117-121
24Gerdes J,Lemke H,Baisch H,Wacker HH,Schwab U,Stein H.Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.J Immunol1984;133:1710-1715
25Preusser M,Heinzl H,Gelpi E,Hftberger R,Fischer I,Pipp I,Milenkovic I,Whrer A,Popovici F,Wolfsberger S,Hainfellner JA.Ki67index in intra-cranial ependymoma:a promising histopathological candidate biomarker.Histopathology2008;53:39-47
26Igarashi N,Takahashi M,Ohkubo H,Omata K,Iida R,Fujimoto S.Predictive value of Ki-67,p53pro-tein,and DNA content in the diagnosis of gastric carcinoma.Cancer1999;86:1449-1454
27Forones NM,Carvalho AP,Giannotti-Filho O,Lou-reno LG,Oshima CT.Cell proliferation and apop-tosis in gastric cancer and intestinal metaplasia.Arq Gastroenterol2005;42:30-34
28Tut VM,Braithwaite KL,Angus B,Neal DE,Lunec J,Mellon JK.Cyclin D1expression in transitional cell carcinoma of the bladder:correlation with p53,waf1,pRb and Ki67.Br J Cancer2001;84:270-275
29郁岩杰,赵治国,于泳,任景丽,王宪远,虎建恩,弋晓萍,温静,冯常炜,李振峰,唐芙爱.萎缩性胃炎伴肠上皮化生浅表隆起灶黏膜中Reg4和Ki67表达高于浅表凹陷灶黏膜.肿瘤2011;31:937-941
30黄永辉,周丽雅,林三仁,金珠,刘建军,丁士刚,夏志伟,段丽萍,常红.放大内镜下胃小凹形态学分类及其临床病理意义.中国内镜杂志2004;10:14-16,19