胃癌螺旋CT征象与Ezrin、E-cadherin蛋白表达间关系的研究
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摘要
背景和目的:
胃癌(gastric cancer)是消化道最常见的恶性肿瘤之一,具有较强的侵袭生长能力,其浸润转移是胃癌治疗失败和病人死亡的主要原因。因此,研究胃癌浸润转移的外在表现及其分子生物学机制,一直是影像、病理及肿瘤分子生物学等领域中的重要课题。螺旋CT(spiral CT,SCT)增强扫描能清晰地显示肿瘤的浸润和转移,是胃癌有效的检查方法。埃兹蛋白(Ezrin)是一种膜-细胞骨架连接蛋白,在许多肿瘤中表达上调,通过与细胞黏附分子相互作用、参与Rho信号传导以及受体酪氨酸激酶信号传导途径等多种机制,参与肿瘤的发生发展。E-粘钙素(E-cadherin)普遍存在于各种上皮细胞中,是肿瘤抑制物的组织特异性细胞黏附分子,在多数肿瘤组织中表达降低。本研究将胃癌的SCT征象与Ezrin、E-cadherin蛋白表达相对照,旨在探讨胃癌SCT表现与分子生物学之间的关系,研究胃癌浸润转移的生物学特征。
材料与方法:
2006年2月至2007年11月间,郑州大学第一附属医院57例胃癌病人,术前行SCT增强扫描。扫描前10min肌肉注射盐酸山良菪碱20mg,口服温开水800-1000ml。对比剂欧乃派克或欧乃影100ml(300mgI/ml),注射速度3ml/s,分别于对比剂注射开始后25s,65s及2-3min采集图像。螺旋CT扫描参数为120KV,240mAs,准直5mm(平扫及静脉期为10mm),螺距均为1,重建厚度5mm。术后全部标本经10%中性缓冲福尔马林固定,石蜡包埋,4Mm连续切片。采用免疫组化SP法检测57例胃腺癌组织中Ezrin、E-cadherin蛋白表达。实验数据采用SPSS11.0软件包进行处理,计数资料采用x~2检验,相关分析采用Spearman等级相关分析,一致性检验采用Kappa分析。以α=0.05为显著性检验水准。
结果:
1.螺旋CT检出了全部57例肿瘤。螺旋CT对胃癌TNM分期的珍断中,T_2与T_(3-4)期正确率为86.0%(49/57),淋巴结有无转移正确率为84.2%(48/57)。螺旋CT和病理检查对于肿瘤T分期、淋巴结转移的诊断,经Kappa检验,两种方法有很好的一致性,说明螺旋CT的诊断结果是可信的(P值＜0.001)。
2.在57例胃癌中,Ezrin蛋白阳性表达50例,阳性表达率为87.7%。在SCT征象上胃癌T分期中,T_2组和T_(3-4)组Ezrin蛋白阳性表达率分别为55.6%(5/9)和93.8%(45/48),两组比较差异有统计学意义(P＜0.05);T_2组和T_(3-4)组Ezrin蛋白过度表达率分别为11.1%(1/9)、41.7%(20/48),两组比较差异有统计学意义(P＜0.05)。在SCT征象上淋巴结转移阳性组和阴性组中,Ezrin蛋白阳性表达率分别为100%(35/35)和68.2%(15/22),两组比较差异具有统计学意义(P＜0.05);Ezrin蛋白过度表达率分别为54.3%(19/35)、9.1%(2/22),两组比较差异有统计学意义(P＜0.05)。
3.在57例胃癌中,E-cadherin蛋白阳性表达21例,阳性表达率为36.8%。在SCT征象上胃癌T分期中,T_2组和T_(3-4)组E-cadherin蛋白阳性表达率分别为77.8%(7/9)和29.2%(14/48),两组比较差异有统计学意义(P＜0.05);T_2组和T_(3-4)组E-cadherin蛋白异常表达率分别为44.4%(4/9)、91.7%(44/48),两组比较差异具有统计学意义(P＜0.05)。在SCT征象上淋巴结转移阳性组和阴性组中,E-cadherin蛋白阳性表达率分别为20.0%(7/35)和63.6%(14/22),两组比较差异具有统计学意义(P＜0.05);E-cadherin蛋白异常表达率分别为94.3%(33/35)和68.2%(15/22),两组比较差异具有统计学意义(P＜0.05)。
4.Ezrin和E-cadherin在胃癌中表达呈负相关性(r_s=-0.474,P=-0.000)。
结论:
1.SCT增强扫描能较全面显示胃癌影像特征,并能较确切反映其病理基础,是胃癌可靠的检查方法。
2.Ezrin蛋白高表达和E-cadherin蛋白低表达与胃癌SCT征象上的肿瘤浸润深度及淋巴结转移相关,提示Ezrin、E-cadherin在胃癌中的表达情况与胃癌的发生、发展及转移具有相关性。
3.胃癌中Ezrin表达与E-cadherin表达呈负相关,提示Ezrin蛋白高表达和E-cadherin蛋白低表达在胃癌的发展中相互作用。
4.胃癌SCT征象与Ezrin、E-cadherin表达相结合,可以从宏观和微观两方面了解胃癌,有助于对胃癌浸润、转移和预后的正确评估,为临床选择治疗方案提供有价值的理论依据。
Background and purpose:
Gastric cancer is one of the most common malignant tumors in digestive tract, which has strong ability of vasion , and the infiltration、metastasis of tumor cell is the main reason of the death of patients, also is the reason of the treatment failure. Investigating the relationship between outwards appearance and molecular mechanism in the development and metastasis of gastric cancer ,therefore, is significant to radiology, pathology and molecular biology. As an effective technic in the examination of the gastric cancer, contrast spiral CT can display the invasion and metastasis of tumor distinctly. Ezrin is a membrane-cytoskeleton linking protein, and its overexpression or alteration of subcelluar localization has been found in many human cancers. Through interacting with adhesion molecules and mediating Rho signaling as well as receptor tyrosine kinase signaling pathways,ezrin plays an important role in cancer development and progression.E-cadherin is the most important tumor suppressor adhesion molecules which is ubiquitous in all kinds of epithelial cells,and the expression of E-cadherin is depressed in most tissues of canaer.The study compared SCT signs with the expression of Ezrin and E-cadherin to investigate the relationship between pathology,molecular biology and SCT appearance of gastric cancer,and to study biologic characteristics of infiltration and metastasis of gastric cancer.
Materials and methods:
57 patients with gastric cancer were performed SCT plain scans and contrast-enhanced scans before operation.20mg 654-2 was injected intramuscularly 10 minutes before the scanning and 800-1000ml lukewarm water was taken. After plain scan contrast-enhanced scans were performed, 100ml constrast medium (Omnipaque or Ultravist 300mgI/ml) was injected via cubital vein with a speed of 3ml/s, the triphasic enhanced scans were obtained at 25s ,65s and 2-3min after the beginning of injection. Scan was performed with 120Kv,240mAs,5-10mm collimation and pitch=1, reconstruction depth 5mm.After operation ,all the specimens were fixed in 10% neutral formalin and embedded in paraffin, 4μm thickness sect serial sections,4 pieces were collected per sample , immunohistochemical stain of Ezrin、E-cadherin and HE stain were perform respectively. Statistical analysis was performed with SPSS 11.0 software , X~2 test was used in numeration data,Spearman correlation from ranks analysis was used in correlation analysis and Kappa analysis was used in consistency checking.Test of significance was consider as a=0.05.
Results:
1. All lesions could be accurately detected by SCT. In all patients, the accuracy of SCT for T and N staging was 86.0%(49/57) and 84.2%(48/57). There were significant differences between SCT and pathologic diagnosis (P< 0.001) .
2. In 57 cases, Ezrin positive-expression was detected in 50 patients.The Ezrin positive rate was 87.7%. In the T_2 staging and T_(3-4) staging in SCT features, the positive rates of Ezrin were 55.6% (5/9) and 93.8% (45/48) respectively, and the difference between the two groups had statistical significance (P<0.05) .In the group with lymph node metastasis and the group without lymph node metastasis in SCT features, the positive rates of Ezrin were 100%(35/35)and 68.2%( 15/22)respectively and there was statistical significance between the two groups (P<0.05) .
3. In 57 cases, E-cadherin positive-expression was detected in 21 patients.The E-cadherin positive rate was 87.7%. In the T_2 staging and T_(3-4) staging in SCT features, the positive rates of E-cadherin were 77.8% (7/9) and 29.2% (14/48) respectively, and the difference between the two groups had statistical significance (P <0.05) .In the group with lymph node metastasis and the group without lymph node metastasis in SCT features, the positive rates of E-cadherin were 20.0% (7/35) and 63.6% (14/22) respectively and there was statistical significance between the two groups (P<0.05) .
4. The expression of Ezrin was negative correlation with the expression of E-cadherinin in gastric cancer (r_s=-0.474, P=0.000) .
Conclusions:
1. SCT contrast-enhanced scan was a credible exanination. It could well display the imaging features and the molecular pathologic basement of gastric cancer.
2. The high expression of Ezrin and the low expression of E-cadherin was closely associated with the deepness of infiltration and the lymph node metastasis in SCT features.It indicates that Ezrin and E-cadherin play promotion roles in the infiltration and metastasis of gastric cancer.
3. The expression of Ezrin was negative correlation with the expression of E-cadherinin in gastric cancer, which suggested that the high expression of Ezrin and the low expression of E-cadherin were correlated with the progression of e gastric cancer.
4. The combination of SCT features and the expression of Ezrin and E-cadherin can help us to know the characteristics of gastric cancer ,and assess the infiltration,metastasis and prognostic correctly,also can help for choosing the optimal method in patient's therapy.
胃癌(gastric cancer)是消化道最常见的恶性肿瘤之一,具有较强的侵袭生长能力,其浸润转移是胃癌治疗失败和病人死亡的主要原因。因此,研究胃癌浸润转移的外在表现及其分子生物学机制,一直是影像、病理及肿瘤分子生物学等领域中的重要课题。螺旋CT(spiral CT,SCT)增强扫描能清晰地显示肿瘤的浸润和转移,是胃癌有效的检查方法。埃兹蛋白(Ezrin)是一种膜-细胞骨架连接蛋白,在许多肿瘤中表达上调,通过与细胞黏附分子相互作用、参与Rho信号传导以及受体酪氨酸激酶信号传导途径等多种机制,参与肿瘤的发生发展。E-粘钙素(E-cadherin)普遍存在于各种上皮细胞中,是肿瘤抑制物的组织特异性细胞黏附分子,在多数肿瘤组织中表达降低。本研究将胃癌的SCT征象与Ezrin、E-cadherin蛋白表达相对照,旨在探讨胃癌SCT表现与分子生物学之间的关系,研究胃癌浸润转移的生物学特征。
材料与方法:
2006年2月至2007年11月间,郑州大学第一附属医院57例胃癌病人,术前行SCT增强扫描。扫描前10min肌肉注射盐酸山良菪碱20mg,口服温开水800-1000ml。对比剂欧乃派克或欧乃影100ml(300mgI/ml),注射速度3ml/s,分别于对比剂注射开始后25s,65s及2-3min采集图像。螺旋CT扫描参数为120KV,240mAs,准直5mm(平扫及静脉期为10mm),螺距均为1,重建厚度5mm。术后全部标本经10%中性缓冲福尔马林固定,石蜡包埋,4Mm连续切片。采用免疫组化SP法检测57例胃腺癌组织中Ezrin、E-cadherin蛋白表达。实验数据采用SPSS11.0软件包进行处理,计数资料采用x~2检验,相关分析采用Spearman等级相关分析,一致性检验采用Kappa分析。以α=0.05为显著性检验水准。
结果:
1.螺旋CT检出了全部57例肿瘤。螺旋CT对胃癌TNM分期的珍断中,T_2与T_(3-4)期正确率为86.0%(49/57),淋巴结有无转移正确率为84.2%(48/57)。螺旋CT和病理检查对于肿瘤T分期、淋巴结转移的诊断,经Kappa检验,两种方法有很好的一致性,说明螺旋CT的诊断结果是可信的(P值＜0.001)。
2.在57例胃癌中,Ezrin蛋白阳性表达50例,阳性表达率为87.7%。在SCT征象上胃癌T分期中,T_2组和T_(3-4)组Ezrin蛋白阳性表达率分别为55.6%(5/9)和93.8%(45/48),两组比较差异有统计学意义(P＜0.05);T_2组和T_(3-4)组Ezrin蛋白过度表达率分别为11.1%(1/9)、41.7%(20/48),两组比较差异有统计学意义(P＜0.05)。在SCT征象上淋巴结转移阳性组和阴性组中,Ezrin蛋白阳性表达率分别为100%(35/35)和68.2%(15/22),两组比较差异具有统计学意义(P＜0.05);Ezrin蛋白过度表达率分别为54.3%(19/35)、9.1%(2/22),两组比较差异有统计学意义(P＜0.05)。
3.在57例胃癌中,E-cadherin蛋白阳性表达21例,阳性表达率为36.8%。在SCT征象上胃癌T分期中,T_2组和T_(3-4)组E-cadherin蛋白阳性表达率分别为77.8%(7/9)和29.2%(14/48),两组比较差异有统计学意义(P＜0.05);T_2组和T_(3-4)组E-cadherin蛋白异常表达率分别为44.4%(4/9)、91.7%(44/48),两组比较差异具有统计学意义(P＜0.05)。在SCT征象上淋巴结转移阳性组和阴性组中,E-cadherin蛋白阳性表达率分别为20.0%(7/35)和63.6%(14/22),两组比较差异具有统计学意义(P＜0.05);E-cadherin蛋白异常表达率分别为94.3%(33/35)和68.2%(15/22),两组比较差异具有统计学意义(P＜0.05)。
4.Ezrin和E-cadherin在胃癌中表达呈负相关性(r_s=-0.474,P=-0.000)。
结论:
1.SCT增强扫描能较全面显示胃癌影像特征,并能较确切反映其病理基础,是胃癌可靠的检查方法。
2.Ezrin蛋白高表达和E-cadherin蛋白低表达与胃癌SCT征象上的肿瘤浸润深度及淋巴结转移相关,提示Ezrin、E-cadherin在胃癌中的表达情况与胃癌的发生、发展及转移具有相关性。
3.胃癌中Ezrin表达与E-cadherin表达呈负相关,提示Ezrin蛋白高表达和E-cadherin蛋白低表达在胃癌的发展中相互作用。
4.胃癌SCT征象与Ezrin、E-cadherin表达相结合,可以从宏观和微观两方面了解胃癌,有助于对胃癌浸润、转移和预后的正确评估,为临床选择治疗方案提供有价值的理论依据。
Background and purpose:
Gastric cancer is one of the most common malignant tumors in digestive tract, which has strong ability of vasion , and the infiltration、metastasis of tumor cell is the main reason of the death of patients, also is the reason of the treatment failure. Investigating the relationship between outwards appearance and molecular mechanism in the development and metastasis of gastric cancer ,therefore, is significant to radiology, pathology and molecular biology. As an effective technic in the examination of the gastric cancer, contrast spiral CT can display the invasion and metastasis of tumor distinctly. Ezrin is a membrane-cytoskeleton linking protein, and its overexpression or alteration of subcelluar localization has been found in many human cancers. Through interacting with adhesion molecules and mediating Rho signaling as well as receptor tyrosine kinase signaling pathways,ezrin plays an important role in cancer development and progression.E-cadherin is the most important tumor suppressor adhesion molecules which is ubiquitous in all kinds of epithelial cells,and the expression of E-cadherin is depressed in most tissues of canaer.The study compared SCT signs with the expression of Ezrin and E-cadherin to investigate the relationship between pathology,molecular biology and SCT appearance of gastric cancer,and to study biologic characteristics of infiltration and metastasis of gastric cancer.
Materials and methods:
57 patients with gastric cancer were performed SCT plain scans and contrast-enhanced scans before operation.20mg 654-2 was injected intramuscularly 10 minutes before the scanning and 800-1000ml lukewarm water was taken. After plain scan contrast-enhanced scans were performed, 100ml constrast medium (Omnipaque or Ultravist 300mgI/ml) was injected via cubital vein with a speed of 3ml/s, the triphasic enhanced scans were obtained at 25s ,65s and 2-3min after the beginning of injection. Scan was performed with 120Kv,240mAs,5-10mm collimation and pitch=1, reconstruction depth 5mm.After operation ,all the specimens were fixed in 10% neutral formalin and embedded in paraffin, 4μm thickness sect serial sections,4 pieces were collected per sample , immunohistochemical stain of Ezrin、E-cadherin and HE stain were perform respectively. Statistical analysis was performed with SPSS 11.0 software , X~2 test was used in numeration data,Spearman correlation from ranks analysis was used in correlation analysis and Kappa analysis was used in consistency checking.Test of significance was consider as a=0.05.
Results:
1. All lesions could be accurately detected by SCT. In all patients, the accuracy of SCT for T and N staging was 86.0%(49/57) and 84.2%(48/57). There were significant differences between SCT and pathologic diagnosis (P< 0.001) .
2. In 57 cases, Ezrin positive-expression was detected in 50 patients.The Ezrin positive rate was 87.7%. In the T_2 staging and T_(3-4) staging in SCT features, the positive rates of Ezrin were 55.6% (5/9) and 93.8% (45/48) respectively, and the difference between the two groups had statistical significance (P<0.05) .In the group with lymph node metastasis and the group without lymph node metastasis in SCT features, the positive rates of Ezrin were 100%(35/35)and 68.2%( 15/22)respectively and there was statistical significance between the two groups (P<0.05) .
3. In 57 cases, E-cadherin positive-expression was detected in 21 patients.The E-cadherin positive rate was 87.7%. In the T_2 staging and T_(3-4) staging in SCT features, the positive rates of E-cadherin were 77.8% (7/9) and 29.2% (14/48) respectively, and the difference between the two groups had statistical significance (P <0.05) .In the group with lymph node metastasis and the group without lymph node metastasis in SCT features, the positive rates of E-cadherin were 20.0% (7/35) and 63.6% (14/22) respectively and there was statistical significance between the two groups (P<0.05) .
4. The expression of Ezrin was negative correlation with the expression of E-cadherinin in gastric cancer (r_s=-0.474, P=0.000) .
Conclusions:
1. SCT contrast-enhanced scan was a credible exanination. It could well display the imaging features and the molecular pathologic basement of gastric cancer.
2. The high expression of Ezrin and the low expression of E-cadherin was closely associated with the deepness of infiltration and the lymph node metastasis in SCT features.It indicates that Ezrin and E-cadherin play promotion roles in the infiltration and metastasis of gastric cancer.
3. The expression of Ezrin was negative correlation with the expression of E-cadherinin in gastric cancer, which suggested that the high expression of Ezrin and the low expression of E-cadherin were correlated with the progression of e gastric cancer.
4. The combination of SCT features and the expression of Ezrin and E-cadherin can help us to know the characteristics of gastric cancer ,and assess the infiltration,metastasis and prognostic correctly,also can help for choosing the optimal method in patient's therapy.
引文
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57.Miyanaga A,Gemma A,Ando M,et al.E-cadherin expression and epidermal growth factor receptor mutation status predict outcome in non-small cell lung cancer patients treated with gefitinib[J].Oncol Rep,2008,19(2):377-383.
58.Richmond PJM,Karayiannakis AJ,Xagafuchi A,et al.Aberrant E-cadherin and α-catcnin expression in prostate cancer:correlation with patient survival[J].Cancer Res.1997,57(15):3189-3 193.
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60.Ng T,Parsons M,Hughes WE,et al.Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility.EMBO J,2001,20:2723-2741.
61.Pujuguel P,Del Maestro L,Gautreau A,et a.Ezrin regulates E-cadherin dependent adherens junction assembly through Racl activation[J].Mol Biol Cell,2003,14:2181-2191.
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23.潘自来,张欢,陈克敏,等.胃癌术前分期:影像学比较学研究[J].中国CT和MRI 杂志,2004,2:25-28.
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25.郭华,高剑波,张智栩,等.胃癌螺旋CT征象与手术病理的相关性研究[J].中国医学影像技术.2006,1(22):104-107.
26.Minami M,Kawawuchi N,Itai Y,et al.Gastric tumors:radiologic-pat hologic correlation and accuracy of T staging with dynamic CT[J].Radiology,1999,185:173-178.
27.Takao M,Fukuda T,Iwanaga S,et al.Gastric cancer:evaluation of triphasic spiral CT and radiologic-pathologic correlation[J].J Comput Assist Tomogr,1998,22(2):288-294.
28.Mani NBS,Suri S,Gupta S,et al.Two phase dynamic contrast enhanced CT with water-filling method for staging of gastric carcinoma[J].Clin Imaging,2001,25(1): 38-43.
29.高剑波,郭华,杨学华,等.胃癌TNM分期螺旋CT与病理学的对照研究[J].放射学实践,2006,11(21):1155-1158.
30.郭华,高剑波,杨学华,等.螺旋CT三期增强扫描对进展期胃癌的珍断价值[J].实用放射学杂志,2006,22(9):1059-1062.
31.Cho JS,Kim JK,Rho SM,et al.Preoperative assessment of gastric carcinoma:value of two-phase dynamic CT with mechanical iv.injection of contrast material[J].A JR Am J Roentgenol.1994,163(1 ):69-75.
32.DuxM,Ritchter GM,hansmann J,et al.helical hydro - CT for diagnosis and staging of gastric carcinoma[J].J Comput Assist Tomogr,1999,23:913 - 922.
33.Hundt W,Braunschweig R,Reiser M.Elvaluation of spiral CT in staging of colon and rectum carcinoma[J].Eur Radiol,1999,9:178-184.
34.罗娅红,于韬.螺旋CT对进展期胃癌的局部浸润和淋巴结转移的研究[J].辽宁医学杂志,2004,18(5):231-233.
35.O'Brien M,Flynn D.Mullins B.et al.Expression of RHOGTPase regulators in human myometrium[J].Reprod Biol Endocrinol.2008,6(1 ):1 - 14.
36.Naba A,Reverdy C,Louvard D,et al.Spatial recruitment and activation of the Fes kinase by ezrin promotes HGF-induced cell scattering[J].Crit Rev Oncol Hematol,2003,46:165-186.
37.Polesello C,Payre F.Small is beautiful:what flies tell us about ERM protein function in development[J].EMBO J,2008,27(1):38-50.
38.Bretscher A.Regulation of cortical structure by the ezrin-radixin-moesin protein family[J].Curr Opin Cell Biol,1999,11(1):109.
39.Bal N,Yildirim S,Nursal TZ,et al.Association of ezrin expression in intestinal and diffuse gastric carcinoma with clinicopathological parameters and tumor type.[J].World J Gastroenterol.2007,13(27):3726-3729.
40.MeClatchey AL.Merlin and ERM proteins:unappreciated roles in cancer development? Nat Rev Cancer,2003,3:877-883.
41.Lan M,Kojima T,Murata M,et al.Phosphorylation of ezrin enhances lnicrovillus length via a p38 MAP-kinase pathway in an immortalized mouse hepatic cell line.Exp Cell Res,2006,312:111-120.
42.Harrison G M,Davies G,Martin T A,et al.Distribution and expression of CD44isoforms and Ezrin during prostate cancer endothelium interaction[J].Int J Oncol, 2002,21:935.
43.Jayaraman B,Nicholson LK.Thermodynamic dissection of the Ezrin FERM/CERMAD interface[J].Biochemistry,2007,46(43):12174-12189.
44.Yu Y,Khan J,Khanna C,et al.Expression profiling identifies the cytoskel etalorganizer ezrin and the developmental homeoprotein Six-1 askey metastatic regulators[J].Nat Med,2004,10(2):175-181.
45.李琼,吴明富,宋安萍,等.浸润性乳腺导管癌组织中Ezrin和钙粘素E的表达与淋巴结转移的关系[J].癌症,2006,25(3):363-366.
46.Chen Z,Fadiel A,Feng Y,et al.Ovarian epithelial carcinoma tyrosine phosphorylation,cell proliferation,and ezrin translocation are stimulated by interleukin 1 alpha and epidermal growth factor[J].Cancer,2001,92:3068
47.Martin T A,Harrison G,Mansel R E,et al.The role of the CD44/ezrin complex in cancer matastasis[J].Crit Rev Oncol Hematol,2003,46(2):165-186.
48.葛杰,陈子华,陈志康,等.CDX2和E-钙粘附素在胃癌组织中的表达及临床意义[J].南方医科大学学报,2008,28(2):279-281.
49.Muretto P,Ruzzo A,Pizzagalli F,et al.Endogastric capsule for E-cadherin gene (CDH1) promoter hypermethylation assessment in DNA from gastric juice of diffuse gastric cancer patients[J].Ann Oncol,2008,19(3):516-519.
50.Shapiro L,Fannon AM,Kwong PD,et al.Structural basis of cell-cell adhesion by cadherins[J].Nature,1995,374(6520):327.
51.傅诚强.E-cadherin及其相关蛋白catenins与癌肿浸涧和转移[J].国外医学外科学分册,1996,23(5):283-285.
52.Bornman DM,Mathew S,Alsrnhe.J,et al.Methylation of the E-cadherin gene bladder neoplasia and in normal nrothelial expression from eldividuals[J].Am J pathol,2001,159(3):834.
53.Dorudi S,Sheffield JP,Poulsom R,et al.E-cadherin expression in colorectal cancer,an immunocytochemical and in situ hybridization study[J].Am J Path,1993,142(2):981-986.
54.Wakatsuki SJ,Watanabe R,Saito K,et al.Loss of human E-cadherin(E-CD)correlated with invasiveness of transitional cell cancer in the renal pelvis,urter and urinary bladder[J].Cancer Lett,1996,103(1):11 - 17.
55.Best S,Sawers Y,Fu VX,et al.Integrity of prostatic tissue for molecular analysis after robotic-assisted laparoscopic and open prostatectomy[J].Urology. 2007,70(2):328-332.
56.Li Z,Wang L,Zhang W,et al.Restoring E-cadherin-mediated cell-cell adhesion increases PTEN protein level and stability in human breast carcinoma cells[J].Biochem Biophys Res Commun.2007,363(1):165-170.
57.Miyanaga A,Gemma A,Ando M,et al.E-cadherin expression and epidermal growth factor receptor mutation status predict outcome in non-small cell lung cancer patients treated with gefitinib[J].Oncol Rep,2008,19(2):377-383.
58.Richmond PJM,Karayiannakis AJ,Xagafuchi A,et al.Aberrant E-cadherin and α-catcnin expression in prostate cancer:correlation with patient survival[J].Cancer Res.1997,57(15):3189-3 193.
59.邵春奎,朱正纲,苏祖兰,等.胃癌组织中p53、c-erbB-2、nm23、E-cadherin基因表达及预后价值[J].癌症,2000,19(7):666-670.
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