Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations
Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations
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DOI：
10.1007/s004280050373
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发表时间：
1999-06-01
期刊：
影响因子：
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通讯作者：
Hofler, H
中科院分区：
文献类型：
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作者：
Schuhmacher, C;Becker, I;Hofler, H
E-钙粘蛋白是一种跨膜细胞粘附分子，在几种类型的癌中观察到其免疫反应性改变。在小叶乳腺癌中，免疫反应性的丧失已被证明是由于E-钙粘蛋白基因的框外缺失或无义突变。应用HEC-D1抗体对29例结肠癌全切除标本进行免疫组化分析。正常蛋白表达相似，在邻近的非恶性粘膜中被认为是在6例，而23肿瘤减少或缺乏E-钙粘蛋白表达。对8例免疫组化显示E-cadherin无表达的病例进行E-cadherin cDNA全序列分析。在这些病例中，尽管免疫组化呈阴性，但序列分析未能揭示任何cDNA突变。这种差异的可能解释包括E-钙粘蛋白启动子的调控缺陷、翻译或蛋白质加工水平的异常以及cDNA分析未研究的基因其他部分的突变（例如内含子序列），这些突变可能在导致E-钙粘蛋白异常加工中发挥作用。
E-cadherin, a transmembrane cell adhesion molecule, has been observed to have an altered pattern of immunoreactivity in several types of carcinomas. In lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with immunohistochemistry using the HEC-D1 antibody. Normal protein expression similar to that in the adjacent nonmalignant mucosa was seen in 6 cases, whereas 23 tumours had reduced or absent E-cadherin expression. In the 8 cases with no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis failed to reveal any cDNA mutations despite the negative immunohistochemistry. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein processing levels and mutations in other parts of the gene that were not investigated by the cDNA analysis (e.g. intronic sequences), which could play a role in causing abnormal processing of the E-cadherin protein.