title: Beta4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer.
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.
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Diaz
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Welch
authors.forename: Terry L
authors.initials: TL
authors.lastname: Smith
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Nour
authors.initials: N
authors.lastname: Sneige
authors.forename: Aysegul A
authors.initials: AA
authors.lastname: Sahin
authors.forename: Michael Z
authors.initials: MZ
authors.lastname: Gilcrease
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D039161:Integrin alpha6beta4 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D000097794:Kalinin
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D039161:Integrin alpha6beta4; D021122:Protein Subunits; D012333:RNA, Messenger; D000097794:Kalinin