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乳腺癌患者 RASSF1A 的甲基化状态和蛋白表达。

Methylation status and protein expression of RASSF1A in breast cancer patients.

机构信息

Clinical Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt,

出版信息

Mol Biol Rep. 2014 Jan;41(1):57-65. doi: 10.1007/s11033-013-2837-3. Epub 2013 Nov 20.

Abstract

Recently genetics and epigenetics alterations have been found to be characteristic of malignancy and hence can be used as targets for detection of neoplasia. RAS association domain family protein 1A (RASSF1A) gene hypermethylation has been a subject of interest in recent researches on cancer breast patients. The aim of the present study was to evaluate whether RASSF1A methylation status and RASSF1A protein expression are associated with the major clinico-pathological parameters. One hundred and twenty breast cancer Egyptian patients and 100-control subjects diagnosed with benign lesions of the breast were enrolled in this study. We evaluated RASSF1A methylation status in tissue and serum samples using Methyl specific PCR together with RASSF1A protein expression in tissues by immunohistochemistry. Results were studied in relation to known prognostic clinicopathological features in breast cancer. Frequency of RASSF1A methylation in tissues and serum were 70 and 63.3 % respectively and RASSF1A protein expression showed frequency of 46.7 %. There was an association between RASSF1A methylation in tissues, serum and loss of protein expression in tissues with invasive carcinoma, advanced stage breast cancer, L.N. metastasis, ER/PR and HER2 negativity. RASSF1A methylation in serum showed high degree of concordance with methylation in tissues (Kappa = 0.851, P < 0.001). RASSF1A hypermethylation in tissues and serum and its protein expression may be a valid, reliable and sensitive tool for detection and follow up of breast cancer patients.

摘要

最近的遗传学和表观遗传学改变被发现是恶性肿瘤的特征,因此可以作为肿瘤检测的靶点。RAS 相关结构域家族蛋白 1A(RASSF1A)基因甲基化是近年来乳腺癌患者癌症研究的热点。本研究旨在评估 RASSF1A 甲基化状态和 RASSF1A 蛋白表达是否与主要临床病理参数相关。本研究纳入了 120 例埃及乳腺癌患者和 100 例经诊断为乳腺良性病变的对照者。我们使用甲基特异性聚合酶链反应(MSP)评估组织和血清样本中的 RASSF1A 甲基化状态,并通过免疫组织化学评估组织中的 RASSF1A 蛋白表达。结果与乳腺癌已知的预后临床病理特征相关联。组织和血清中 RASSF1A 甲基化的频率分别为 70%和 63.3%,RASSF1A 蛋白表达的频率为 46.7%。组织中 RASSF1A 甲基化、血清和组织中蛋白表达缺失与浸润性癌、晚期乳腺癌、淋巴结转移、ER/PR 和 HER2 阴性有关。血清中 RASSF1A 甲基化与组织中甲基化高度一致(Kappa=0.851,P<0.001)。组织和血清中 RASSF1A 高甲基化及其蛋白表达可能是一种有效的、可靠的、敏感的检测和随访乳腺癌患者的工具。

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