High ERK Protein Expression Levels Correlate with Shorter Survival in Triple-Negative Breast Cancer Patients

The mitogen-activated protein kinase (MAPK) signaling pathway is known to be activated in triple-negative breast cancer (TNBC). Extracellular signal-related kinase (ERK), a member of the MAPK pathway, promotes cell proliferation, angiogenesis, cell differentiation, and cell survival. To assess the prognostic impact of ERK in TNBC patients, relative quantities of ERK (ERK-2 and pMAPK) and direct targets of the ERK pathway (MAPK/ERK kinase 1, phospho-enriched protein in astrocytes [PEA]-15, phosphorylated (p)PEA-15, tuberous sclerosis protein 2, p70S6 kinase, and p27) were measured using reverse-phase protein arrays in tumor tissue from patients with TNBC (n = 97) and non-TNBC (n = 223). Protein levels in patients with TNBC were correlated with clinical and tumor characteristics and outcome. The median age of patients with TNBC was 55 years (range, 27-86 years). Disease stage was I in 21%, II in 60%, and III in 20% of the patients. In a multivariate analysis, among patients with TNBC, those with ERK-2-overexpressing tumors had a lower overall survival rate than those with low ERK-2-expressing tumors (hazard ratio [HR], 2.76; 95% confidence interval [CI], 1.19-6.41). However, high pMAPK levels were associated with a significantly higher relapse-free survival rate (HR, 0.66; 95% CI, 0.46-0.95). In conclusion, ERK-2 and pMAPK are valuable prognostic markers in TNBC. Further studies are justified to elucidate ERK's role in TNBC tumorigenicity and metastasis. The Oncologist 2012;17:766-774