β4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer
β4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer
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DOI：
10.1038/modpathol.3800411
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发表时间：
2005-09-01
期刊：
影响因子：
7.5
通讯作者：
Gilcrease, MZ
中科院分区：
文献类型：
--
作者：
Diaz, LK;Cristofanilli, M;Gilcrease, MZ
体外数据支持α6β4整合素在肿瘤细胞迁移和侵袭中的作用，特别是在乳腺癌细胞中，但关于这种潜在重要的整合素的临床数据有限。在乳腺癌的基因芯片分析中，β4整合素亚单位已被证明与基底/肌上皮细胞特有的基因聚集在一起，而基底/肌上皮细胞特有基因表达增加的乳腺癌亚群似乎尤其具有侵袭性。本研究的目的是确定α6β4整合素的表达是否与乳腺癌的侵袭性临床病理特征有关，以及该整合素的表达在早期乳腺癌中是否具有预后意义。我们用原位杂交法检测了一组早期浸润性乳腺癌患者中β4整合素亚单位基因在肿瘤中的表达，并将其表达水平与多种临床病理特征相关联。我们还评估了层粘连蛋白-5蛋白在该患者队列中的表达，层粘连蛋白-5是α6β4的主要配体。尽管我们观察到β4基因高表达和层粘连蛋白5共表达的患者的无病生存率略有下降的趋势，但这并未达到统计学意义(P=0.11)。然而，我们确实观察到β4mRNA的表达与肿瘤大小(P=0.01)和肿瘤核分级(P
In vitro data support a role for the alpha 6 beta 4 integrin in tumor cell migration and invasion, particularly in breast carcinoma cells, but clinical data on this potentially important integrin are limited. The beta 4 integrin subunit has been shown to cluster with genes characteristic of basal/myoepithelial cells in cDNA microarray analyses of breast cancer, and the subset of breast cancers with increased expression of genes characteristic of basal/myoepithelial cells appears to be particularly aggressive. The purpose of this study was to determine whether alpha 6 beta 4 integrin expression correlates with aggressive clinicopathologic features of breast cancer and whether expression of this integrin has prognostic significance in early breast cancer. We evaluated tumor expression of the beta 4 integrin subunit gene in a cohort of patients with early invasive breast carcinoma by in situ hybridization and correlated expression levels with multiple clinicopathologic characteristics. We also evaluated expression of laminin-5 protein, the principal ligand of alpha 6 beta 4, in this patient cohort. Although we observed a slight trend towards decreased disease-free survival for patients whose tumors had high beta 4 gene expression and coexpression of laminin-5, this did not reach statistical significance (P=0.11). However, we did observe a correlation between beta 4 mRNA expression and both tumor size (P=0.01) and tumor nuclear grade (P