title: Increased phosphorylation of ERK1/2 is associated with worse chemotherapeutic outcome and a poor prognosis in advanced lung adenocarcinoma.
abstract: Constitutive activation of extracellular signal-regulated kinase (ERK)1/2 pathway, that is activated by various stimuli including growth factors and oncogenic driver mutations, is observed in various cancers. However, the difference of the activated levels of the pathway is still unclear in clinical significances. The aim of this study was to investigate the effect of different ERK1/2 pathway activation, assessed by the expression levels of phosphorylated (p) ERK1/2, on the prognosis of advanced lung adenocarcinoma patients. Paraffin-embedded lung biopsy samples were obtained from 85 lung adenocarcinoma patients. Correlation between pERK1/2 expression levels that were assessed by immunohistochemistry (IHC) analysis and oncogenic driver mutation status, clinicopathological factors, outcome from standard anticancer therapies, and prognosis was investigated. Varying levels of pERK1/2 expression were observed in 68 (80.0 %) patients. The overall survival was significantly reduced in patients with higher pERK1/2 expression in comparison to those with lower expression levels (P = 0.03). In particular, higher pERK1/2 expression levels correlated with worse performance status and worse clinical outcome. Thus, the IHC analysis of pERK1/2 expression levels may predict patient prognosis in advanced lung adenocarcinoma. Inhibition of ERK1/2 pathway activated by various signals may improve the effects of standard chemotherapies and the clinical condition of patients with advanced cancer.
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan. tsujino.ichiro@nihon-u.ac.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsujino
authors.affiliation: Division of Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Hiranuma
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Division of Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hirotani
authors.affiliation: Division of Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Sumie
authors.initials: S
authors.lastname: Ohni
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ouchi
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Division of Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Norimichi
authors.initials: N
authors.lastname: Nemoto
authors.affiliation: Division of Respiratory Medicine, Department of Internal Medicine, Nihon University School of Medicine, 30-1, Ohyaguchikamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Hashimoto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Chemotherapy; EGFR; KRAS; Lung adenocarcinoma; Prognosis; pERK1/2