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Tumor Biology

, Volume 35, Issue 7, pp 6455–6465 | Cite as

Extracellular signal-regulated kinase (ERK) expression and activation in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival

  • Stamatios TheocharisEmail author
  • Ioly Kotta-Loizou
  • Jerzy Klijanienko
  • Constantinos Giaginis
  • Paraskevi Alexandrou
  • Eougken Dana
  • Jose Rodriguez
  • Efstratios Patsouris
  • Xavier Sastre-Garau
Research Article

Abstract

Extracellular signal-regulated kinase (ERK) has been considered as a critical regulator of diverse cellular processes such as proliferation, survival and motility, being implicated in the malignant transformation in several tissue types. The present study aimed to evaluate the clinical significance of total ERK1 (t-ERK1) and phosphorylated ERK1/2 (p-ERK1/2) protein expression in mobile tongue squamous cell carcinoma (SCC). t-ERK1 and p-ERK1/2 protein expression in tumour cells and infiltrating the tumour microenvironment lymphoid cells was assessed immunohistochemically on 47 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics, overall and disease-free patients’ survival. Enhanced nuclear t-ERK1 and p-ERK1/2 expression in tumour cells was associated with the absence of perineural invasion (p = 0.043) and shorter overall patients’ survival (log-rank test, p = 0.028), respectively. Enhanced t-ERK1 expression in infiltrating lymphoid cells was significantly associated with female gender, absence of vascular and perineural invasion, lymph node metastases and early depth of invasion (p = 0.008, p = 0.019, p = 0.011, p = 0.036 and p = 0.001, respectively), as well as with longer disease-free survival times (log-rank test, p = 0.038). Enhanced p-ERK1/2 expression in infiltrating lymphoid cells was significantly associated with the presence of vascular invasion and lymph node metastases (p = 0.019 and p = 0.004, respectively) and shorter overall patients’ survival (log-rank test, p = 0.013). In multivariate analysis, p-ERK1/2 expression in tumour cells and infiltrating lymphoid cells was identified as independent prognostic factors of overall survival (Cox regression analysis, p = 0.045 and p = 0.032, respectively). The present study supported evidence that ERK signalling pathway may exert a potential role in the pathophysiological aspects of the mobile tongue SCC, presenting also potential utility as a biomarker for patients’ survival and reinforcing the development of novel anti-cancer therapies targeting ERK signalling cascade in this type of human malignancy.

Keywords

Mobile tongue squamous cell carcinoma ERK1 p-ERK1/2 Clinicopathological parameters Prognosis Immunohistochemistry 

Notes

Conflicts of interest

All authors verify that they have not accepted any funding or support from an organization that may in any way gain or lose financially from the results of the present study. All authors verify that they have not been employed by an organization that may in any way gain or lose financially from the results of the present study. None of the authors have any other conflicting interest.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Stamatios Theocharis
    • 1
    • 2
    Email author
  • Ioly Kotta-Loizou
    • 2
  • Jerzy Klijanienko
    • 1
  • Constantinos Giaginis
    • 2
    • 3
  • Paraskevi Alexandrou
    • 2
  • Eougken Dana
    • 2
  • Jose Rodriguez
    • 4
  • Efstratios Patsouris
    • 2
  • Xavier Sastre-Garau
    • 1
  1. 1.Department of PathologyInstitut CurieParisFrance
  2. 2.First Department of Pathology, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
  3. 3.Department of Food Science and NutritionUniversity of the AegeanLemnosGreece
  4. 4.Department of Head and Neck SurgeryInstitut CurieParisFrance

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