β4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer

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<0.01). These results do not demonstrate prognostic significance for beta 4 gene expression and/or laminin-5 protein expression in early breast cancer, but increased beta 4 gene expression in larger tumors and in higher grade tumors does support a potential role for the alpha 6 beta 4 integrin in tumor progression.