title: High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype.
abstract: Focal adhesion kinase (FAK) is a protein tyrosine kinase expressed in invasive breast cancer that regulates antiapoptotic signaling. We have examined FAK expression by immunohistochemistry using anti-FAK 4.47 in breast tumor samples from a large population-based, case-control study of women participating in the University of North Carolina Breast Specialized Programs of Research Excellence (SPORE), Carolina Breast Cancer Study. In this population, 629 formalin-fixed, paraffin-embedded tissue sections were stained for FAK and scored as high (3+ or 4+ intensity and > or = 90% positive cells) or otherwise. High FAK expression was associated with poor prognostic indicators including high mitotic index (>10 mitoses per 10 consecutive high-power fields), nuclear grade 3, architectural grade 3, estrogen and progesterone receptor negative, and HER-2/neu overexpressed using CB11 antibody. The association of high FAK expression with HER-2/neu overexpression lends further support that HER-2/neu and FAK collaborate to promote tumorigenesis. The presence of strong FAK expression in many high grade, estrogen- and progesterone-negative breast carcinomas indicates that FAK may be an attractive target for therapeutic intervention.
authors.affiliation: Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Lark
authors.forename: Chad A
authors.initials: CA
authors.lastname: Livasy
authors.forename: Lynn
authors.initials: L
authors.lastname: Dressler
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Joseph
authors.initials: J
authors.lastname: Geradts
authors.forename: Mary
authors.initials: M
authors.lastname: Iacocca
authors.forename: David
authors.initials: D
authors.lastname: Cowan
authors.forename: Debbie
authors.initials: D
authors.lastname: Little
authors.forename: Rolf J
authors.initials: RJ
authors.lastname: Craven
authors.forename: William
authors.initials: W
authors.lastname: Cance
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness
chemical_list: D014408:Biomarkers, Tumor; D051416:Focal Adhesion Protein-Tyrosine Kinases