Cytoplasmic expression of E-cadherin and β-Catenin correlated with LOH and hypermethylation of the APC gene in oral squamous cell carcinomas
Cytoplasmic expression of E-cadherin and β-Catenin correlated with LOH and hypermethylation of the APC gene in oral squamous cell carcinomas
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DOI：
10.1111/j.1600-0714.2004.00275.x
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发表时间：
2005-02-01
影响因子：
3.3
通讯作者：
Sorensen, JA
中科院分区：
文献类型：
--
作者：
Gao, S;Eiberg, H;Sorensen, JA
背景：大肠腺瘤性息肉病（APC）基因失活导致β -连环蛋白的积累和易位，这对恶性发展很重要。本研究的目的是探讨APC/ β -连环蛋白通路在口腔鳞状细胞癌中的可能作用。方法：采用甲基化特异性聚合酶链反应（MS-PCR）检测34例患者的DNA，检测APC周围两个标记的杂合性缺失（LOH），以及APC启动子的高甲基化。34个样本中有15个进行免疫组织化学染色，显示E-cadherin和β - catenin的表达。结果：我们发现E-cadherin和β - catenin的细胞质染色而不是膜染色是肿瘤相关的显著异常改变，并且这种表达主要存在于中分化和低分化的肿瘤中。APC启动子的LOH和高甲基化分别出现在31个癌样本中的4个和34个癌样本中的5个。免疫组化（IHC）染色显示，5例LOH/高甲基化患者中有4例细胞质表达E-cadherin和β - catenin。结论：APC基因座的缺失或APC启动子1a的高甲基化可能导致口腔癌细胞胞质中游离β -连环蛋白的积累，从而导致口腔恶性进展。
BACKGROUND: Inactivation of the adenomatous polyposis coli (APC) gene results in accumulation and translocation of beta-Catenin, which are important for malignant development. The aim of the present study is to investigate the possible role of APC/beta-Catenin pathway in oral squamous cell carcinomas.METHODS: The DNA from 34 patients was examined for loss of heterozygosity (LOH) at two markers surrounding the APC, and for hypermethylation of the APC promoter by using methylation-specific polymerase chain reaction (MS-PCR). Fifteen of 34 samples were stained immunohistochemically to show the expression of E-cadherin and beta-Catenin.RESULTS: We found that cytoplasmic rather than membrane staining of E-cadherin and beta-Catenin was a prominent aberrant tumour-related alteration, and that this expression was mainly present in moderately and poorly differentiated tumours. LOH and hypermethylation of the APC promoter was found in four of 31 and five of 34 carcinoma samples, respectively. Four of five cases presenting LOH/hypermethylation showed cytoplasmic expression of E-cadherin and beta-Catenin by immunohistochemical (IHC) staining.CONCLUSION: The present results indicate that LOH at the APC locus or hypermethylation of the APC promoter 1a may lead to free beta-Catenin accumulation in cytoplasm of oral carcinoma cells and thereby to oral malignant progression.