Expression and Mutation Pattern of β-Catenin and Adenomatous Polyposis Coli in Colorectal Cancer Patients
Expression and Mutation Pattern of β-Catenin and Adenomatous Polyposis Coli in Colorectal Cancer Patients
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DOI：
10.1016/j.arcmed.2015.01.001
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发表时间：
2015-01-01
影响因子：
7.7
通讯作者：
Mokdad-Gargouri, Raja
中科院分区：
文献类型：
--
作者：
Abdelmaksoud-Damak, Rania;Miladi-Abdennadher, Imen;Mokdad-Gargouri, Raja
背景和安斯。 β-连环蛋白和腺瘤性息肉病大肠杆菌 (APC) 是 Wnt 通路的主要组成部分。本研究旨在探讨结直肠癌（CRC）患者肿瘤和淋巴结中β-连环蛋白和APC的表达以及编码这些蛋白的基因的突变谱。方法。在 124 个肿瘤和 41 个淋巴结中检测了 APC 和 β-连环蛋白的表达。通过PCR测序筛选CTNNBI的外显子3和APC基因的外显子15的突变簇区域(MCR)是否存在突变。结果。在肿瘤和淋巴结中分别检测到 58.1% 和 48.8% 的 β-连环蛋白的核/细胞质免疫染色。在肿瘤中，β-连环蛋白的异常表达与肿瘤大小和淋巴结中的肿瘤大小相关。膜 β-连环蛋白表达分别出现在 41.9% 和 14.6% 的肿瘤和淋巴结中。在肿瘤中，膜性β-连环蛋白的缺乏与高侵袭性和转移潜力相关。分别在 2% 和 14% 的肿瘤和淋巴结中观察到 APC 免疫染色阳性。细胞核/细胞质中的过度表达和膜β-连环蛋白的缺乏与总生存率的降低显着相关。在 25 个肿瘤中，有 4 个存在 Ser33 和 Ser47 突变，并在细胞核/细胞质中过度表达 β-连环蛋白。在 13 个肿瘤的 APC 基因中发现了突变，其中 6 个突变是新的。结论。观察到肿瘤细胞核/细胞质中β-连环蛋白的异常表达与淋巴结之间呈正相关。 β-连环蛋白的细胞核/细胞质积累和膜表达丧失与存活率降低有关，可作为候选预后预测因子。 (C) 2015 年IMSS。由爱思唯尔公司出版
Background and Anns. beta-Catenin and adenomatous polyposis coli (APC) are major components of the Wnt pathway. This study aimed to investigate the expression of beta-catenin and APC in tumors and lymph nodes in colorectal cancer (CRC) patients and the mutational spectrum of the genes coding these proteins.Methods. Expression of APC and beta-catenin was examined in 124 tumors and 41 lymph nodes. Exon 3 of CTNNBI and the mutation cluster region (MCR) in exon 15 of the APC gene were screened for mutation by PCR-sequencing.Results. Nuclear/cytoplasmic immunostaining of beta-catenin was detected in 58.1 and 48.8% in tumors and lymph nodes, respectively. In tumors, abnormal expression of beta-catenin correlated with tumor size and with those in lymph nodes. Membranous beta-catenin expression occurred in 41.9 and 14.6% of tumors and lymph nodes, respectively. In tumors, lack of membranous beta-catenin correlated with high invasiveness and metastatic potential. Positive immunostaining for APC was observed in 2 and 14% of tumors and lymph nodes, respectively. Overexpression in nucleus/cytoplasm and lack of membranous beta-catenin significantly correlated with a reduced overall survival. Among 25 tumors, four harbour mutation in Ser33 and Ser47 and overexpress the beta-catenin in the nucleus/cytoplasm. Mutations were identified in the APC gene in 13 tumors and six mutations were novel.Conclusions. Positive association between aberrant expression of beta-catenin in the nucleus/cytoplasm of tumors and lymph nodes was observed. Nucleus/cytoplasmic accumulation of beta-catenin and loss of membranous expression are related to reduced survival and could serve as a candidate prognostic predictor. (C) 2015 IMSS. Published by Elsevier Inc.