Study of phospho-β-catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome
Study of phospho-β-catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome
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DOI：
10.1038/modpathol.3800562
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发表时间：
2006-04-01
期刊：
影响因子：
7.5
通讯作者：
Keramopoulos, A
中科院分区：
文献类型：
--
作者：
Nakopoulou, L;Mylona, E;Keramopoulos, A
β-连环蛋白在细胞间粘附中发挥着至关重要的作用，并且作为 Wnt 通路的成员也发挥着信号传导作用。本研究的目的是检查磷酸化β-连环蛋白在乳腺癌中的临床病理学和预后价值及其与肿瘤表型的关系。对 141 份石蜡包埋的乳腺组织标本进行免疫组织化学检测，检测磷酸-β-连环蛋白、ER、PR、c-erbB-2、p53、Ki-67、bcl-2、uPAR 和 TIMP-1。对于每种情况，通过图像分析确定磷酸-β-连环蛋白指数。在恶性细胞的细胞质和细胞核中检测到磷酸-β-连环蛋白染色。在肿瘤较小（P = 0.030）、分期较低（P = 0.026）、Ki-67 降低和 c-erbB-2 免疫反应性高（分别为 P = 0.052 和 P = 0.037）的癌症中，细胞质磷酸-β-连环蛋白具有统计学意义较高。核磷酸-β-连环蛋白与 ER 和 ER β（分别为 P = 0.022 和 P = 0.043）、bcl-2（P = 0.042）、癌细胞中的 uPAR（P = 0.041）和 TIMP-1 呈平行相关，尽管相关性处于临界状态（P = 0.066）。研究发现，细胞质磷酸-β-连环蛋白与延长的无病生存期和总生存期独立相关（分别为 P = 0.046 和 P = 0.002），而核定位与缩短的总生存期相关（P = 0.046）。总之，根据其亚细胞分布，磷酸-β-连环蛋白可能在浸润性乳腺癌中有不同的参与。核定位似乎与侵袭性肿瘤表型相关，对患者的总体生存产生负面影响，而细胞质定位与有利的肿瘤表型以及更长的无病生存和总体生存相关。
beta-Catenin has a crucial role in cell-cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated beta-catenin, as well as its relation to the tumors' phenotype, in breast cancer. Immunohistochemistry was applied on 141 paraffin-embedded breast tissue specimens for the detection of phospho-beta-catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and TIMP-1. For each case, a phospho-beta-catenin index was determined by image analysis. Phospho-beta-catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho-beta-catenin was statistically higher in carcinomas of smaller tumor size (P = 0.030), lower stage (P = 0.026), decreased Ki-67 and high c-erbB-2 immunoreactivity (P = 0.052 and P = 0.037, respectively). Nuclear phospho-beta-catenin showed a parallel correlation with ER and ER beta (P = 0.022 and P = 0.043, respectively), bcl-2 (P = 0.042), uPAR in cancer cells (P = 0.041) and TIMP-1, although the correlation was borderline (P = 0.066). Cytoplasmic phospho-beta-catenin was found to be independently correlated with prolonged disease-free and overall survival (P = 0.046 and P = 0.002, respectively), whereas nuclear localization was correlated with a shortened overall survival (P = 0.046). In conclusion, phospho-beta-catenin may have a different involvement in invasive breast carcinomas, according to its subcellular distribution. Nuclear localization seems to be related to an aggressive tumor phenotype, negatively affecting patients' overall survival, whereas cytoplasmic localization is associated with a favorable tumor phenotype and a longer disease-free and overall survival.