title: Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis.
abstract: Focal adhesion kinase (FAK) is a protein tyrosine kinase that is overexpressed in a subset of invasive breast cancers. FAK transmits signals that mediate several functions including tumor cell proliferation, migration, adhesion and survival. We used immunohistochemical techniques to assess FAK expression in patients with fibrocystic disease (FCD), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC). Formalin-fixed, paraffin-embedded (FFPE) tissue sections were obtained from 119 patients (12 FCD, 38 ADH, 51 DCIS and 18 IDC). The anti-FAK 4.47 monoclonal antibody was used to detect FAK expression. FAK expression was scored as high (3 or 4 intensity and > or =90% positive cells) or low. The DCIS tissue sections demonstrated high FAK expression in 34/51 (66%) of the sections. High FAK expression was demonstrated in 6/18 (33%) of the IDC tissue sections and 8/38 (21%) of the ADH tissue sections. None (0/12) of the FCD tissues sections stained high for FAK. The pattern of FAK expression in DCIS was significantly higher than ADH (p < 0.0001) and IDC (p = 0.02). We conclude that FAK overexpression in preinvasive, DCIS tumors precedes tumor cell invasion or metastasis, suggesting that FAK may function as a survival signal and be an early event in breast tumorigenesis.
authors.affiliation: Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Harry M
authors.initials: HM
authors.lastname: Lightfoot
authors.forename: Amy
authors.initials: A
authors.lastname: Lark
authors.forename: Chad A
authors.initials: CA
authors.lastname: Livasy
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: David
authors.initials: D
authors.lastname: Cowan
authors.forename: Lynn
authors.initials: L
authors.lastname: Dressler
authors.forename: Rolf J
authors.initials: RJ
authors.lastname: Craven
authors.forename: William G
authors.initials: WG
authors.lastname: Cance
mesh_terms: D001941:Breast Diseases / Q000201:enzymology / Q000503:physiopathology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000503:physiopathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology* / Q000503:physiopathology*; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D005260:Female; D005348:Fibrocystic Breast Disease / Q000201:enzymology / Q000503:physiopathology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020869:Gene Expression Profiling; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human