title: High expression of focal adhesion kinase (p125FAK) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome.
abstract: BACKGROUND
  Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-negative breast cancer it is important to identify high-risk patients who would benefit from further adjuvant therapy.
  
  
  METHODS
  We analyzed 162 node-negative breast cancer cases to determine the prognostic relevance of FAK expression, and we investigated the relationship of FAK with major associated signaling pathways (HER2, Src, Akt and extracellular regulated kinases) by immunohistochemistry and western blot analysis.
  
  
  RESULTS
  Elevated FAK expression did not predict patient outcome, in contrast to tumor grading (P = 0.005), Akt activation (P = 0.0383) and estrogen receptor status (P = 0.0033). Significant positive correlations were observed between elevated FAK expression and HER2 overexpression (P = 0.001), as well as phospho-Src Tyr-215 (P = 0.021) and phospho-Akt (P < 0.001), but not with phospho-ERK1/2 (P = 0.108). Western blot analysis showed a significant correlation of FAK Tyr-861 activation and HER2 overexpression (P = 0.01).
  
  
  CONCLUSIONS
  Immunohistochemical detection of FAK expression is of no prognostic significance in node-negative breast cancer but provides evidence that HER2 is involved in tumor malignancy and metastatic ability of breast cancer through a novel signaling pathway participating FAK and Src.
authors.affiliation: Institute of Pathology, University Hospital of Essen-Duisburg, Essen, Germany. klaus.schmitz@uni-essen.de
authors.forename: Klaus Jürgen
authors.initials: KJ
authors.lastname: Schmitz
authors.forename: Florian
authors.initials: F
authors.lastname: Grabellus
authors.forename: Rainer
authors.initials: R
authors.lastname: Callies
authors.forename: Friedrich
authors.initials: F
authors.lastname: Otterbach
authors.forename: Jeremias
authors.initials: J
authors.lastname: Wohlschlaeger
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.forename: Rainer
authors.initials: R
authors.lastname: Kimmig
authors.forename: Kurt Werner
authors.initials: KW
authors.lastname: Schmid
authors.forename: Hideo Andreas
authors.initials: HA
authors.lastname: Baba
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D018570:Risk Assessment; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D051417:Focal Adhesion Kinase 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051058:Oncogene Protein v-akt; D018719:Erb-b2 Receptor Tyrosine Kinases
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