Loss of E-cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance
Loss of E-cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance
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DOI：
10.1002/cncr.10211
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发表时间：
2002-01-15
期刊：
影响因子：
6.2
通讯作者：
Yuen, APW
中科院分区：
文献类型：
--
作者：
Chang, HW;Chow, V;Yuen, APW
背景E-钙粘蛋白表达于正常上皮细胞的表面，在癌症中已经发现E-钙粘蛋白表达的缺失，并且假定其促进肿瘤细胞解离和转移。本研究旨在探讨舌鳞癌组织中E-cadherin基因启动子区密集甲基化在E-cadherin表达下调中的作用。109例口腔舌癌上皮钙粘蛋白的表达（93例原发性肿瘤，7例局部复发性肿瘤和9例转移性淋巴结）通过肿瘤组织的免疫组织化学染色进行评价，F-cadherin启动子区5个Hpa Ⅱ侧翼CpG岛甲基化状态的研究用甲基化敏感的聚合酶链反应对86例肿瘤进行了甲基化敏感的限制性内切酶（methylation sensitive restriction enzyme）酶切位点的评价（70例原发性肿瘤，7例局部复发性肿瘤和9例转移性淋巴结）。E-cadherin在83%的原发性肿瘤、86%的复发性肿瘤和89%的淋巴结转移中表达不足。在64%的原发性肿瘤、71%的复发性肿瘤和67%的淋巴结转移瘤中发现了高甲基化的E-钙粘蛋白启动子。E-cadherin表达下调与启动子甲基化有关。在原发肿瘤、相应的转移淋巴结和复发肿瘤中，E-cadherin基因启动子区甲基化均呈弱表达，E-cadherin基因表达下调是影响患者预后的一个重要因素。启动子区CpG位点的甲基化在抑制原发性口腔舌癌及其相应的复发和淋巴结转移中的E-cadherin表达中起关键作用。由此导致的E-钙粘蛋白表达下调对初次手术治疗的患者的预后有不良影响。(C)2002年美国癌症协会。
BACKGROUND. E-cadherin is expressed on the surface of normal epithelial cells, Loss of E-cadherin expression has been found in cancers and is postulated to facilitate tumor cell dissociation and metastasis. This study evaluated the role of promoter dense methylation in the downregulation of E-cadherin expression in oral tongue carcinoma.METHODS. E-cadherin expression of 109 oral tongue carcinomas (93 primary tumors, 7 locally recurrent tumors, and 9 metastatic lymph nodes) was evaluated by immunohistochemical staining of tumor tissues, The methylation status of the CpG islands at the promoter region of F-cadherin which flanked five HpaII (methylation sensitive restriction enzyme) digestion sites were evaluated by methylation sensitive polymerase chain reaction in 86 tumors (70 primary, tumors, 7 locally recurrent tumors, and 9 metastatic lymph nodes).RESULTS. Underexpression of E-cadherin was found in 83% of primary tumors, 86% of recurrent tumors, and 89% of nodal metastases. Hypermethylated E-cadherin promoter was found in 64% of primary tumors, 71% of recurrent tumors, and 67% of nodal metastases. Downregulation of E-cadherin expression was found to be related to promoter hypormethylation. Consistently weak expression of E-cadherin by promoter hypermethylation was observed in primary tumors, their corresponding metastatic lymph nodes, and recurrent tumors, Downregulation of E-cadherin expression was a significant poor prognostic factor for survival.CONCLUSIONS. Methylation of CpG sites at the promoter region played a key role in the inhibition of E-cadherin expression in both primary oral tongue carcinomas and their corresponding recurrences and nodal metastases. The resulting downregulation of E-cadherin expression had adverse effects on the prognosis, of patients who were treated by primary surgery. (C) 2002 American Cancer Society.