Overexpression of activated phospholipase C1 is a risk factor for distant metastases in T1-T2, N0 breast cancer patients undergoing adjuvant chemotherapy
International Journal of Cancer, 08/03/2012
Lattanzio R et al. – PLCgamma1 over-expression appears to be a reliable predictive surrogate marker of development of metastases. Thus, targeting PLCgamma1 pathways might represent a potential therapeutic approach for the prevention of metastatic disease in breast cancer.Methods
- The aim of our study is to evaluate the association between the expression of PLCgamma1, and of PLCgamma1 phosphorylated at Tyr1253 (PLCgamma1-pY1253) and at Tyr783 (PLCgamma1-pY783) with the clinical outcome of patients with node negative, T1/T2 breast cancers.
- The study groups consisted of 292 (training set) and 122 (validation set) patients presenting with primary unilateral breast carcinoma (T1-2), with no evidence of nodal involvement and distant metastases.
- PLCgamma1, PLCgamma1-pY1253, and PLCgamma1-pY783 protein expression were assessed by immunohistochemistry on tissue microarrays, and the results correlated with the clinical data using Kaplan–Meier curves and multivariate Cox regression analysis.
- Tumor cells while expressing variable proportions of cytoplasmic PLCgamma1, express PLCgamma1-pY1253, and PLCgamma1-pY783 predominantly in the nucleus.
- High expression of PLCgamma1, and of its activated forms, is associated with a worse clinical outcome in terms of incidence of distant metastases, and not of local relapse in T1-T2, N0 breast cancer patients undergone adjuvant chemotherapy.