PLC-gamma-1 phosphorylation status is prognostic of metastatic risk in patients with early-stage Luminal-A and -B breast cancer subtypes

BackgroundPhospholipase C gamma 1 (PLC gamma 1) is highly expressed in human tumours. Our previous studies reported that both stable and inducible PLC gamma 1 down-regulation can inhibit formation of breast-cancer-derived experimental lung metastasis. Further, high expression of PLC gamma 1 and its constitutively activated forms (i.e., PLC gamma 1-pY1253, PLC gamma 1-pY783) is associated with worse clinical outcome in terms of incidence of distant metastases, but not of local relapse in T1-T2, N0 breast cancer patients.MethodsIn the present retrospective study, we analysed the prognostic role of PLC gamma 1 in early breast cancer patients stratified according to the St. Gallen criteria and to their menopausal status. PLC gamma 1-pY1253 and PLC gamma 1-pY783 protein expression levels were determined by immunohistochemistry on tissue microarrays, and were correlated with patients' clinical data, using univariate and multivariate statistical analyses.ResultsIn our series, the prognostic value of PLC gamma 1 overexpression was restricted to Luminal type tumours. From multivariate analyses, pY1253-PLC gamma 1(High) was an independent prognostic factor only in postmenopausal patients with Luminal-B tumours (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.1-5.3; P=0.034). Conversely, PLC gamma 1-pY783(High) was a remarkably strong risk factor (HR, 20.1; 95% CI, 2.2-178.4; P=0.003) for pre/perimenopausal patients with Luminal-A tumours.ConclusionsPLC gamma 1 overexpression is a strong predictive surrogate marker of development of metastases in early Luminal-A and -B breast cancer patients, being able to discriminate patients with high and low risk of metastases. Therefore, targeting the PLC gamma 1 pathway can be considered of potential benefit for prevention of metastatic disease.