Diaz Leslie K, Cristofanilli Massimo, Zhou Xiao, Welch Kristin L, Smith Terry L, Yang Ying, Sneige Nour, Sahin Aysegul A, Gilcrease Michael Z
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mod Pathol. 2005 Sep;18(9):1165-75. doi: 10.1038/modpathol.3800411.
In vitro data support a role for the alpha6beta4 integrin in tumor cell migration and invasion, particularly in breast carcinoma cells, but clinical data on this potentially important integrin are limited. The beta4 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 alpha6beta4 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 beta4 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 alpha6beta4, in this patient cohort. Although we observed a slight trend towards decreased disease-free survival for patients whose tumors had high beta4 gene expression and coexpression of laminin-5, this did not reach statistical significance (P=0.11). However, we did observe a correlation between beta4 mRNA expression and both tumor size (P=0.01) and tumor nuclear grade (P<0.01). These results do not demonstrate prognostic significance for beta4 gene expression and/or laminin-5 protein expression in early breast cancer, but increased beta4 gene expression in larger tumors and in higher grade tumors does support a potential role for the alpha6beta4 integrin in tumor progression.
体外实验数据表明α6β4整合素在肿瘤细胞迁移和侵袭中发挥作用，尤其是在乳腺癌细胞中，但关于这种潜在重要整合素的临床数据有限。在乳腺癌的cDNA微阵列分析中，β4整合素亚基已被证明与基底/肌上皮细胞特征性基因聚集，而具有基底/肌上皮细胞特征性基因表达增加的乳腺癌子集似乎具有特别强的侵袭性。本研究的目的是确定α6β4整合素表达是否与乳腺癌侵袭性临床病理特征相关，以及该整合素的表达在早期乳腺癌中是否具有预后意义。我们通过原位杂交评估了一组早期浸润性乳腺癌患者肿瘤中β4整合素亚基基因的表达，并将表达水平与多种临床病理特征相关联。我们还评估了该患者队列中α6β4的主要配体层粘连蛋白-5蛋白的表达。尽管我们观察到肿瘤β4基因高表达且层粘连蛋白-5共表达的患者无病生存期有轻微下降趋势，但这未达到统计学意义（P = 0.11）。然而，我们确实观察到β4 mRNA表达与肿瘤大小（P = 0.01）和肿瘤核分级（P < 0.01）均相关。这些结果并未证明β4基因表达和/或层粘连蛋白-5蛋白表达在早期乳腺癌中的预后意义，但在较大肿瘤和高级别肿瘤中β4基因表达增加确实支持α6β4整合素在肿瘤进展中可能发挥的作用。
