Expression of E-cadherin, α-catenin, β-catenin, and CD44 (Standard and variant isoforms) in human cholangiocarcinoma:: An immunohistochemical study
Expression of E-cadherin, α-catenin, β-catenin, and CD44 (Standard and variant isoforms) in human cholangiocarcinoma:: An immunohistochemical study
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DOI：
10.1002/hep.510270412
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发表时间：
1998-04-01
期刊：
影响因子：
13.5
通讯作者：
Kaibara, N
中科院分区：
文献类型：
--
作者：
Ashida, K;Terada, T;Kaibara, N
E-钙粘附素(E-cad)、α-连环素、β-连环素和CD44在胆管细胞癌中的免疫定位研究很少。因此，我们用免疫组织化学方法检测了E-cad、α-catenin、β-catenin、CD44标准(CD44s)和CD44v5、CD44v6、CD44v7-8、CD44v10等CD44变异体(CD44v5、CD44v6、CD44v7-8和CD44v10)在正常成人肝脏和47例CC中的表达，并将结果与肿瘤分级、血管侵袭、转移、p53表达、增殖分数(Ki-67标记)和c-erbB2表达相关联。在正常肝组织中，E-cad、α-连环蛋白和β-连环蛋白在正常肝内胆管细胞膜上均有表达，而CD44s、CD44v5、CD44v6、CD44v7-8和CD44v10均不表达。在大多数CC中，E-cad、α-catenin和β-catenin的膜表达与非癌胆管相同或降低。我们发现E-cad、α-catenin和β-catenin的表达下调与肿瘤的高级别显著相关，而与肿瘤的血管侵袭、转移、p53表达、Ki-67标记或c-erbB2表达无关，但β-catenin的下调与c-erbB2的下调有关。CD44s、CD44v5、CD44v6、CD44v7-8和CD44v10仅在CC细胞膜上频繁表达。CD44的异常表达与肿瘤分级、转移、血管侵犯、P53表达、Ki-67标记和c-erbB2表达无明显相关性，但CD44s和CD44v5的表达与肿瘤分级、转移、血管侵犯、p53表达、Ki-67标记和c-erbB2表达无明显相关性。我们发现CD44s的异常表达与无转移和血管侵犯显著相关，CD44v5的异常表达与P53的低表达显著相关。提示E-cad、α-catenin和β-catenin在大多数CC中的膜表达降低，这种下调与CC的高级别有关，而β-catenin的下调与c-erbB2的下调有关。这些结果还提示CD44s、CD44v5、CD44v6、CD44v7-8和CD44v10在CC的发生过程中可能有新的表达，但这种新表达与CC的进展无关，CD44s和CD44v5除外。
Immunolocalization of E-cadherin (E-cad), alpha-catenin, beta-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, alpha-catenin, beta-catenin, CD44 standard (CD44s), and CD44 variants (CDS tv) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, alpha-catenin and beta-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, alpha-catenin, and beta-catenin was the same or reduced when compared with noncancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, alpha-catenin, and beta-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for beta-catenin, the down-regulation of which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 mere frequently expressed at the membrane of CC cells. There mere, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, alpha-catenin, and beta-catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that beta-catenin down-regulation is associated with c-erbB2 down-regulation, The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and CD44v5.