Is Expression or Activation of Src Kinase Associated with Cancer-Specific Survival in ER-, PR- and HER2-Negative Breast Cancer Patients?

Elsberger, B., Tan, B., Brown, S., Mitchell, T., Mallon, E., Tovey, S., Brunton, V., Cooke, T. and Edwards, J. (2009) Is Expression or Activation of Src Kinase Associated with Cancer-Specific Survival in ER-, PR- and HER2-Negative Breast Cancer Patients? American Journal of Pathology, 175(4), pp. 1389-1397. (doi: 10.2353/ajpath.2009.090273)

Abstract

The aim of the current study was to assess the expression levels of c-Src and phosphorylated Src kinase in human breast cancers and to establish if these are linked to oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status or patient survival. Tissue microarray technology was used to analyze 314 breast cancer specimens. Immunohistochemistry was performed using antibodies to c-Src, Y419Src, and Y215Src, and expression was assessed using the weighted histoscore method. High cytoplasmic c-Src kinase and high membrane phosphorylated activated Y419Src kinase was associated with decreased disease-specific survival. In contrast, phosphorylated activated nuclear and cytoplasmic Y215Src kinase expression levels were significantly associated with improved disease-specific survival. When the cohort was subdivided according to ER/PR/HER2 status, the ER-negative subgroup (105 patients) was associated with improved disease-specific survival and was found to be independent by multivariate analysis with a hazard ratio of 0.4 (interquartile range 0.2–0.8). High cytoplasmic c-Src expression was associated with decreased survival; high expression of activated c-Src (Y215) was associated with improved survival. This was potentiated in the ER/HER2-negative subgroup. Hence, administration of Src kinase inhibitors aiming to decrease phosphorylation should be approached with caution, especially in ER-negative patients. It is therefore essential to appropriately identify with the correct biomarkers which patients are most likely to respond to Src inhibitors.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Edwards, Professor Joanne and Elsberger, Miss Beatrix and Cooke, Prof Timothy
• Authors: Elsberger, B., Tan, B., Brown, S., Mitchell, T., Mallon, E., Tovey, S., Brunton, V., Cooke, T., and Edwards, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: American Journal of Pathology
• Publisher: American Society for Investigative Pathology
• ISSN: 0002-9440
• ISSN (Online): 1525-2191