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.