Role of Src family members in breast cancer-dependent on site of phosphorylation

Abstract #2074 Background: In vitro work implicates c-Src in breast cancer. However there is little evidence to support this in clinical specimens. Activation of Src family members are associated with phosphorylation at two different tyrosine sites Y419: the classical activation site and Y215, known to induce a 50-fold increase in activation. We have analysed a cohort of human breast cancers to establish if expression levels of 2 Src family members (c-Src and Lyn) are associated with survival and whether this is dependent on site of activation. Methods: Tissue microarrays were constructed from 895 breast cancer tumors. Median follow up was 6 years with 229 breast cancer specific deaths. Immunohistochemistry was performed using antibodies to c-Src, Lyn, pSrc419 and pSrc215 (antibodies to Y419 and Y215 will detect phosphorylation of either c-Src and Lyn). Expression was assessed by two independent scorers. All statistical calculations were performed using SPSS 15. Results: Membrane expression of c-Src and Lyn was rarely observed. However, cytoplasmic expression of c-Src and Lyn was frequently observed and further results presented relate to this site. High expression levels of c-Src but not Lyn were associated with HER2 positivity (p=0.001) and ER negativity (p