Specific up-regulation of FAK expression in primary breast cancer as a marker for malignant transformation

Abstract

9647 Background: The focal adhesion kinase (FAK) is a protein tyrosine kinase linked to integrin mediated cell-cell and cell- matrix signalling and overexpressed in a variety of human solid tumors. FAK expression might be correlated to the invasive and metastatic capability of tumor cells. The data on breast cancer are inconclusive. To determine whether FAK is up-regulated, we analyzed FAK protein levels and expression patterns in primary breast cancer and normal tissue. Methods: To analyze the expression changes of FAK in breast cancer development we determined FAK in 55 matched pairs of breast cancer and corresponding normal tissue of the same patient by Western Blot and immunohistochemistry, using a FAK specific monoclonal antibody. Results: Using a score ranging from 0 to +5 for western blots, we found in normal breast tissue a low median score of 1,00, which was strongly induced up to 3,0 in invasive breast cancers. The medium score was 1,51 ⦡ 0,836 in physiological tissue versus 2,91 ⦡ 1,221 in tumors. A more detailed analysis revealed, that 50 out of 55 normal tissue specimen (90,9%) were valued with a score of 0 to +2. Interestingly, score +1 was given in 30/55 probes or 54,5% of all physiological tissue specimen. Only 5 (9,1%) samples were detected with a score of +3 or +5. In contrast, invasive breast cancer displayed a strong FAK expression. Score +3 to +5 was found in 33/55 (60%) specimen, with 17/55 (30,9%) in the highest two score ranks +4 and +5. Only 7/55 tumors (12,7%) got a score of +1.Overall, 45 out of 55 corresponding tissue pairs (81,8%) were found to show an upregulation of p125FAK protein expression in the tumors in direct comparison to the normal surrounding breast tissue. Immunohistochemistry confirmed the findings of Western Blot analysis. Conclusion: FAK is specifically upregulated in breast cancer in comparison to matched normal breast tissue. These results provide evidence on a large number of specimen that induction of FAK is a frequent and relatively constant event in breast cancer development. FAK might serve as a marker for malignant transformation. No significant financial relationships to disclose.