title: High ERK protein expression levels correlate with shorter survival in triple-negative breast cancer patients.
abstract: 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.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. chbartho@mdanderson.org
authors.forename: Chandra
authors.initials: C
authors.lastname: Bartholomeusz
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Jaime
authors.initials: J
authors.lastname: Ferrer-Lozano
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobágyi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1