胆囊癌组织中CD44V6、E-Cad的表达及其意义
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摘要
目的：通过对胆囊癌中CD44V6、E-Cad的表达检测，探讨他们的表达及其意义。
方法：应用免疫组织化学的方法检测48例胆囊癌、29例胆囊腺瘤性息肉、25例慢性结石性胆囊炎中CD44V6、E-Cad的表达情况，并分析其表达与胆囊癌临床病理的关系。
结果：1．48例胆囊癌中E—Cad阳性表达21例(43.75％)，29例胆囊腺瘤性息肉中阳性表达21例(72.41％)，而25例慢性结石性胆囊炎中阳性表达24例(96.00％)。2．48例胆囊癌中CD44V6阳性表达31例(64.58％)，29例胆囊腺瘤性息肉中阳性表达9例(31.03％)，而25例慢性结石性胆囊炎中阳性表达仅1例(4.00％)。3．E—Cad在胆囊癌中的表达与CD44V6的表达呈负相关(r_s~′=-0.909，P＜0.05)；CD44V6、E-Cad表达与胆囊癌的Nevin分期、组织分化程度、淋巴结转移有关(P＜0.05)，而与患者性别、年龄无明显关系(P＞0.05)。4．CD44V6、E—Cad在胆囊癌、胆囊腺瘤性息肉、慢性结石性胆囊炎中的表达差异均有显著性(P＜0.05)。
结论：胆囊癌中CD44V6过度表达，E-Cad低表达，提示CD44V6在胆囊癌的发生、发展及转移过程中可能起到了促进作用，而E-Cad可能起到抑制作用。二者对预测胆囊癌预后可能有一定意义。
Objective: To investigate the expression of CD44V6 and E-Cad in gallbladder carcinoma and its clinical significance.
Methods: The protein expression of CD44V6 and E-Cad was detected by immunohistochemical technique in 48 cases of gallbladder carcinoma,29 cases of gallbladder adenoma polypi and 25 cases of chronic calculous cholecytitis, and the relationship between their expression with the clinical and pathologic characters of gallbladder carcinoma was analyzed.
Results: 1. E-Cadherin was expressed in 21 of 48(43.75%) cases of gallbladder carcinoma, in 21 of 29(72.41%) cases of gallbladder adenoma polypi and in 24 of 25(96.00%) cases of chronic calculous cholecytitis. 2. CD44V6 was expressed in 31 of 48(64.58%) cases of gallbladder carcinoma, in 9 of 29(31.03%) cases of gallbladder adenoma polypi and in 1 of 25(4.00%) cases of chronic calculous cholecytitis . 3. A negative correlation was noted between expression of CD44V6 and E-Cadherin (rs'=-0.909,/7<0.05) in gallbladder carcinoma. The expression of CD44V6 and E-Cadherin was correlated with the Nevin's stages, cellular differential degrees and lymphnodes metastasis(p<0.05) of gallbladder
carcinoma, whereas it was not correlated with sex and age of the patient(?>0.05) . 4. The expression of CD44V6 and E-Cadherin in these three kinds of tissue was significantly different(/?<0.05).
Conclusion: The over expression of CD44V6 and low expression of E-Cadherin suggest that CD44V6 might be promoted factors of gallbladder carcinoma genesis, development and metastasis, while E-Cadherin might be suppressive factors. It would be helpful for forecasting the prognosis of gallbladder carcinoma by detecting their expression.
方法：应用免疫组织化学的方法检测48例胆囊癌、29例胆囊腺瘤性息肉、25例慢性结石性胆囊炎中CD44V6、E-Cad的表达情况，并分析其表达与胆囊癌临床病理的关系。
结果：1．48例胆囊癌中E—Cad阳性表达21例(43.75％)，29例胆囊腺瘤性息肉中阳性表达21例(72.41％)，而25例慢性结石性胆囊炎中阳性表达24例(96.00％)。2．48例胆囊癌中CD44V6阳性表达31例(64.58％)，29例胆囊腺瘤性息肉中阳性表达9例(31.03％)，而25例慢性结石性胆囊炎中阳性表达仅1例(4.00％)。3．E—Cad在胆囊癌中的表达与CD44V6的表达呈负相关(r_s~′=-0.909，P＜0.05)；CD44V6、E-Cad表达与胆囊癌的Nevin分期、组织分化程度、淋巴结转移有关(P＜0.05)，而与患者性别、年龄无明显关系(P＞0.05)。4．CD44V6、E—Cad在胆囊癌、胆囊腺瘤性息肉、慢性结石性胆囊炎中的表达差异均有显著性(P＜0.05)。
结论：胆囊癌中CD44V6过度表达，E-Cad低表达，提示CD44V6在胆囊癌的发生、发展及转移过程中可能起到了促进作用，而E-Cad可能起到抑制作用。二者对预测胆囊癌预后可能有一定意义。
Objective: To investigate the expression of CD44V6 and E-Cad in gallbladder carcinoma and its clinical significance.
Methods: The protein expression of CD44V6 and E-Cad was detected by immunohistochemical technique in 48 cases of gallbladder carcinoma,29 cases of gallbladder adenoma polypi and 25 cases of chronic calculous cholecytitis, and the relationship between their expression with the clinical and pathologic characters of gallbladder carcinoma was analyzed.
Results: 1. E-Cadherin was expressed in 21 of 48(43.75%) cases of gallbladder carcinoma, in 21 of 29(72.41%) cases of gallbladder adenoma polypi and in 24 of 25(96.00%) cases of chronic calculous cholecytitis. 2. CD44V6 was expressed in 31 of 48(64.58%) cases of gallbladder carcinoma, in 9 of 29(31.03%) cases of gallbladder adenoma polypi and in 1 of 25(4.00%) cases of chronic calculous cholecytitis . 3. A negative correlation was noted between expression of CD44V6 and E-Cadherin (rs'=-0.909,/7<0.05) in gallbladder carcinoma. The expression of CD44V6 and E-Cadherin was correlated with the Nevin's stages, cellular differential degrees and lymphnodes metastasis(p<0.05) of gallbladder
carcinoma, whereas it was not correlated with sex and age of the patient(?>0.05) . 4. The expression of CD44V6 and E-Cadherin in these three kinds of tissue was significantly different(/?<0.05).
Conclusion: The over expression of CD44V6 and low expression of E-Cadherin suggest that CD44V6 might be promoted factors of gallbladder carcinoma genesis, development and metastasis, while E-Cadherin might be suppressive factors. It would be helpful for forecasting the prognosis of gallbladder carcinoma by detecting their expression.
引文
[1] 黄志强。黄志强胆道外科 第一版，山东：山东科学技术出版社，1998：780．
[2] 石景森，周连锁，王作仁，等．肝外胆道癌 830 例临床分析，中华外科杂志，1997,35：645．
[3] VLeminckx K,Vakaet L,Mareel M et al.Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 1991:66:107-119.
[4] Oka S,Shiozake H,Kobayashi K et al.Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis.Cancer Res 1993:53:1696-1701.
[5] Pignatelli M,Ansari TW, Gunter P et al.Loss of membraneous E-cadherin expression in pancreatic cancer:correlation with lymph node metastasis,high grade and advanced stage. J Pathol 1994:174:243-248.
[6] Jawhare A,Jordan S,Poole S et al.Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma:relationship with patient survival.Gastroenterology 1997:112:45-54.
[7] Cowin P.Unraveling the cytoplasmic interaction of the cadherin surperfamily.Pro Natl Acad Sci USA. 1994:91:10759-61.
[8] 刘鹏飞，吴孟超，陈汉，等．原发性肝癌血液CD44v m RNA检测的临床意义．中华肝脏病杂志，1998，6：141．
[9] hert U, Hofmann M,Rudy W, et al. Cell,1991;65:13-24.
[10] Shiozaki H. Oka H.Znoue M, et al. E-Cadherin mediated adhesion system in cancer cells. Cancer, 1996,TT, 1605-1613.
[11] 简卫国，李凌．E-Cadherin 的生物学特征和临床意义，临床与实验病理学杂志，1998，14：502-503。
[12] 苏剑敏，周逸平，徐薇苓．E-钙粘蛋白在四种肿瘤中表达的比较．中华病理
学杂志，2001，25：6．
[13] Hugh TJ,Dillon SA,Taylor BA, et al. caherin-catenin expression in primary colorectal cancer: a survival analysis .Br J Cancer, 1999,80:1046-1051.
[14] Soto F, Shimsda Y, Watanabe G,et al.Expression of Vascular enolothelial growth factor, matrix metalloproteinase-9 and E-cadherin in the process of lymph node metastasis in esophageal cancer. Br J Cancer, 1999,80:1366-1372.
[15] Curiec N,Marcellin L, Gairard B, et al. CD44 exon b expression as a possible early prognostic factor in primary node negative breastCarcinoma[J].Chin Exp Metastasis,1996,14(5):434-439.
[16] Cofuku J, shiozaki H,Jsujinaka T, et al.Expression of E-Cadherin and alphacatenin in patients with colorectal carcinomal correlation with Cancer invasion and metastasis [J].Am J chin pathol, 1999,111 (1):29-37.
[17] Aldridge MC,Brismuth H.Gallbladder cancer:the polyp-cancer sequence.Br J Surg, 1990,77:363.
[18]杨秋霞．赵贤姝．CD44 分子生物学特性及肿瘤关系的研究进展．国外医学免疫学分册,2000,23：1．
[19]黄开红、袁世珍．CD44 表达与消化系肿瘤转移和预后的关系．广州医药，2000,31：2．
[20] Goodison S, Urquide V, Tarin D. CD44 cell adhesion molecules[J]. Mol Pathol,1999,52(4): 189-196.
[21] Yamamichi K ,Vehara Y, Kita mura N, et al. Increased expression of CD44V6 Mma significantly correlates with distant metastasis and poor prognosis in gastric cancer[J].Int J Cancer, 1998,79(3):256-262.
[22]田文等．CD44 表达与肿瘤．中华医学杂志，1997；TT(8)：631-632．
[23]张云锋，王作仁，王林，等．胆囊癌中基质金属蛋白酶表达及其临床意义．中华实验外科杂志,2002,19：5．
[24] Washington K M,Marcia R ,Cottfride M .Expression of the cell adhesion molecule CD44 in gastric adenocarciomas. Human Pathol, 1994,25:1043.
[25]高随宽，徐文怀．CD44 分子与肿瘤．国外医学分子生物学分册，1995，17：127．
[26] Streit M ,Schmide R ,Hilgenfeld RU ,et al.Adhesion receptors in malignant transformation of gastrointestinal tumors[J].J Mol Med, 1996,74:253-268.
[27] Takeichi M.Cadherins:a molecule family important in selective cell-cell adhesion. Ann Rev Biochem 1990:59:237-252.
[28] Eidelman S,Damsky CH, Weelock MJ et al.Expression of the cell-cell adhesion glycoprotein:cell-CAM120/80 in normal human tissues and tumors. Am J Pathol 1989;135:101.
[29] Tamura S,Shiozaki H,Miyata M et al. Decreased E-cadherin expression is associated with haematogenous recurrence and poor prognosis in patient with squamous cell carcinoma of the oesophagus. Br J Surg 1996;83:1608.
[30] Jawhari A,Jordan S,Poole S et al.Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma .Gastroe- ntology. 1997; 112:46-54.
[31]石景森．我国胆囊癌的发展情况及外科处理．肝胆胰外科杂志，1999，11(1)．
[32] Seiter S et al.Expression of CD44 variant proteins in human colorectal cancer is related tumor progression .Cancer Res, 1993;53:4754-4756.
[2] 石景森，周连锁，王作仁，等．肝外胆道癌 830 例临床分析，中华外科杂志，1997,35：645．
[3] VLeminckx K,Vakaet L,Mareel M et al.Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 1991:66:107-119.
[4] Oka S,Shiozake H,Kobayashi K et al.Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis.Cancer Res 1993:53:1696-1701.
[5] Pignatelli M,Ansari TW, Gunter P et al.Loss of membraneous E-cadherin expression in pancreatic cancer:correlation with lymph node metastasis,high grade and advanced stage. J Pathol 1994:174:243-248.
[6] Jawhare A,Jordan S,Poole S et al.Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma:relationship with patient survival.Gastroenterology 1997:112:45-54.
[7] Cowin P.Unraveling the cytoplasmic interaction of the cadherin surperfamily.Pro Natl Acad Sci USA. 1994:91:10759-61.
[8] 刘鹏飞，吴孟超，陈汉，等．原发性肝癌血液CD44v m RNA检测的临床意义．中华肝脏病杂志，1998，6：141．
[9] hert U, Hofmann M,Rudy W, et al. Cell,1991;65:13-24.
[10] Shiozaki H. Oka H.Znoue M, et al. E-Cadherin mediated adhesion system in cancer cells. Cancer, 1996,TT, 1605-1613.
[11] 简卫国，李凌．E-Cadherin 的生物学特征和临床意义，临床与实验病理学杂志，1998，14：502-503。
[12] 苏剑敏，周逸平，徐薇苓．E-钙粘蛋白在四种肿瘤中表达的比较．中华病理
学杂志，2001，25：6．
[13] Hugh TJ,Dillon SA,Taylor BA, et al. caherin-catenin expression in primary colorectal cancer: a survival analysis .Br J Cancer, 1999,80:1046-1051.
[14] Soto F, Shimsda Y, Watanabe G,et al.Expression of Vascular enolothelial growth factor, matrix metalloproteinase-9 and E-cadherin in the process of lymph node metastasis in esophageal cancer. Br J Cancer, 1999,80:1366-1372.
[15] Curiec N,Marcellin L, Gairard B, et al. CD44 exon b expression as a possible early prognostic factor in primary node negative breastCarcinoma[J].Chin Exp Metastasis,1996,14(5):434-439.
[16] Cofuku J, shiozaki H,Jsujinaka T, et al.Expression of E-Cadherin and alphacatenin in patients with colorectal carcinomal correlation with Cancer invasion and metastasis [J].Am J chin pathol, 1999,111 (1):29-37.
[17] Aldridge MC,Brismuth H.Gallbladder cancer:the polyp-cancer sequence.Br J Surg, 1990,77:363.
[18]杨秋霞．赵贤姝．CD44 分子生物学特性及肿瘤关系的研究进展．国外医学免疫学分册,2000,23：1．
[19]黄开红、袁世珍．CD44 表达与消化系肿瘤转移和预后的关系．广州医药，2000,31：2．
[20] Goodison S, Urquide V, Tarin D. CD44 cell adhesion molecules[J]. Mol Pathol,1999,52(4): 189-196.
[21] Yamamichi K ,Vehara Y, Kita mura N, et al. Increased expression of CD44V6 Mma significantly correlates with distant metastasis and poor prognosis in gastric cancer[J].Int J Cancer, 1998,79(3):256-262.
[22]田文等．CD44 表达与肿瘤．中华医学杂志，1997；TT(8)：631-632．
[23]张云锋，王作仁，王林，等．胆囊癌中基质金属蛋白酶表达及其临床意义．中华实验外科杂志,2002,19：5．
[24] Washington K M,Marcia R ,Cottfride M .Expression of the cell adhesion molecule CD44 in gastric adenocarciomas. Human Pathol, 1994,25:1043.
[25]高随宽，徐文怀．CD44 分子与肿瘤．国外医学分子生物学分册，1995，17：127．
[26] Streit M ,Schmide R ,Hilgenfeld RU ,et al.Adhesion receptors in malignant transformation of gastrointestinal tumors[J].J Mol Med, 1996,74:253-268.
[27] Takeichi M.Cadherins:a molecule family important in selective cell-cell adhesion. Ann Rev Biochem 1990:59:237-252.
[28] Eidelman S,Damsky CH, Weelock MJ et al.Expression of the cell-cell adhesion glycoprotein:cell-CAM120/80 in normal human tissues and tumors. Am J Pathol 1989;135:101.
[29] Tamura S,Shiozaki H,Miyata M et al. Decreased E-cadherin expression is associated with haematogenous recurrence and poor prognosis in patient with squamous cell carcinoma of the oesophagus. Br J Surg 1996;83:1608.
[30] Jawhari A,Jordan S,Poole S et al.Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma .Gastroe- ntology. 1997; 112:46-54.
[31]石景森．我国胆囊癌的发展情况及外科处理．肝胆胰外科杂志，1999，11(1)．
[32] Seiter S et al.Expression of CD44 variant proteins in human colorectal cancer is related tumor progression .Cancer Res, 1993;53:4754-4756.