Clinicopathological significance of Y416Src and Y527Src expression in breast cancer

To elucidate the clinicopathological significance of Y416Src and Y527Src expression in breast cancer, and to evaluate their usefulness as potential predictive markers for Src inhibitors.

c-Src is a non-receptor tyrosine kinase; the active form of c-Src can catalyse tyrosine phosphorylation. The expression and activity of c-Src correlates with cell adhesion, survival, angiogenesis, migration, invasion and osteoclast function. There are limited clinicopathological data on Src expression and breast cancer characteristics.

An immunohistochemical study was performed to determine the expression of c-Src, Y416Src, and Y527Src in 215 consecutive breast cancer cases. The correlation of their expression with various clinicopathological factors was analysed statistically.

c-Src was expressed in all 215 cases (100%). Y416Src was expressed in 174 cases (80.9%) and was highly expressed in 30 cases (14.0%). Y527Src was expressed in 138 cases (64.2%) and was highly expressed in 11 cases (5.1%). High expression of Y416Src was significantly associated with metastatic disease (p=0.0327), whereas high expression of Y527Src was significantly associated with metastatic disease (p=0.0004), clinical stage (p=0.0062), as well as HER2 status (p=0.0149). High expression of either Y416Src or Y527Src was significantly correlated with poor overall survival (p=0.0049 and p<0.0001, respectively). In the 192 curatively operated cases, Y416Src expression was significantly associated with poor disease-free survival (p=0.0088).

Although further studies to assess Src activity are necessary, investigation of Src inhibitors for breast cancer including in-vivo models should be encouraged more.