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.
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.
Schmitz
Klaus Jürgen
KJ
Institute of Pathology, University Hospital of Essen-Duisburg, Essen, Germany. klaus.schmitz@uni-essen.de
Grabellus
Florian
F
Callies
Rainer
R
Otterbach
Friedrich
F
Wohlschlaeger
Jeremias
J
Levkau
Bodo
B
Kimmig
Rainer
R
Schmid
Kurt Werner
KW
Baba
Hideo Andreas
HA
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
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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