Original Article

Modern Pathology (2005) 18, 1165–1175. doi:10.1038/modpathol.3800411; published online 27 May 2005

bold italic beta4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer

Leslie K Diaz1, Massimo Cristofanilli2, Xiao Zhou1, Kristin L Welch1, Terry L Smith3, Ying Yang3, Nour Sneige1, Aysegul A Sahin1 and Michael Z Gilcrease1

  1. 1Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
  2. 2Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
  3. 3Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Dr MZ Gilcrease, MD, PhD, Department of Pathology, Box 85, MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. E-mail: mgilcrease@mdanderson.org

Received 5 January 2005; Revised 27 January 2005; Accepted 27 January 2005; Published online 27 May 2005.

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Abstract

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.

Keywords:

alpha6beta4 integrin, in situ hybridization, laminin-5

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