Medical Molecular Morphology

, Volume 49, Issue 2, pp 98–109 | Cite as

Increased phosphorylation of ERK1/2 is associated with worse chemotherapeutic outcome and a poor prognosis in advanced lung adenocarcinoma

  • Ichiro TsujinoEmail author
  • Yoko Nakanishi
  • Hisato Hiranuma
  • Tetsuo Shimizu
  • Yukari Hirotani
  • Sumie Ohni
  • Yasushi Ouchi
  • Noriaki Takahashi
  • Norimichi Nemoto
  • Shu Hashimoto
Original Paper


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.


Lung adenocarcinoma EGFR KRAS pERK1/2 Chemotherapy Prognosis 



This work was supported by Nihon University School of Medicine 50th Anniversary Fund Research Grant (2012–2013).


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Copyright information

© The Japanese Society for Clinical Molecular Morphology 2015

Authors and Affiliations

  • Ichiro Tsujino
    • 1
    Email author
  • Yoko Nakanishi
    • 2
  • Hisato Hiranuma
    • 1
  • Tetsuo Shimizu
    • 1
  • Yukari Hirotani
    • 2
  • Sumie Ohni
    • 2
  • Yasushi Ouchi
    • 1
  • Noriaki Takahashi
    • 1
  • Norimichi Nemoto
    • 2
  • Shu Hashimoto
    • 1
  1. 1.Division of Respiratory Medicine, Department of Internal MedicineNihon University School of MedicineTokyoJapan
  2. 2.Division of Pathology, Department of Pathology and MicrobiologyNihon University School of MedicineTokyoJapan

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