Is there an association with phosphorylation and dephosphorylation of Src kinase at tyrosine 530 and breast cancer patient disease-specific survival

Abstract

Background:Recent work has demonstrated that c-Src and fully activated Y419Src expression was associated with poor clinical outcome of breast cancer patients. It is unknown whether different activation stages of c-Src equally influence disease-specific survival of breast cancer patients.Methods:Immunohistochemistry was performed on 165 resected breast cancers using antibodies to phosphorylated and dephosphorylated Src kinase tyrosine site 530. Expression was assessed using the weighted histoscore method.Results:Majority of phosphorylated and dephosphorylated Y530Src expression was observed in the nucleus and cytoplasm. Only 3.6% of phosphorylated Y530Src (pY530Src) expression was detected in the membrane, compared with 53% with dephosphorylated Y530Src. Nuclear expression of pY530Src correlated negatively with oestrogen receptor (ER) status (χ2 P<0.001), whereas cytoplasmic phosphorylated and dephosphorylated Y530Src expression correlated negatively with membrane c-Src expression (χ2 P=0.008, χ2 P<0.001). On univariate and multivariate analysis, no significant association was noticed between phosphorylated or dephosphorylated Y530Src expression and disease-specific survival at any cellular location.Conclusion:ER-negative breast cancer patients were more likely to express pY530Src in the nucleus. Breast cancer patients with higher cytoplasmic expression of phosphorylated or dephosphorylated Y530Src were more likely not to express c-Src at the membrane. Phosphorylated and dephosphorylated Y530Src expression is not associated with survival of patients.