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Mitogen‐activated protein kinases in gliomas and correlation with patients' prognosis
Author(s) -
Zolota V.,
Sirinian C.,
Kefalopoulou Z.,
Panagiotopoulos V.,
Spinos P.,
Argyriou A. A.,
Kalofonos H. P.
Publication year - 2014
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.12175
Subject(s) - mapk/erk pathway , immunohistochemistry , kinase , p38 mitogen activated protein kinases , glioma , medicine , phosphorylation , oncology , protein kinase a , cohort , mitogen activated protein kinase , univariate analysis , univariate , proportional hazards model , cancer research , multivariate analysis , biology , multivariate statistics , microbiology and biotechnology , statistics , mathematics
Objective We examined the activation of the mitogen‐activated protein kinases ( MAPK s) signaling pathway in a cohort of brain gliomas, by taking advantage of a series of phosphorylation state‐specific antibodies against phospho‐p44/42( ERK 1/2), phospho‐p38, and phospho‐ JNK . Potential correlations between expression profiles of phospho‐p44/42( ERK 1/2), phospho‐p38, and phospho‐ JNK and tumor grade, age, gender, overall survival, and Ki‐67 status were also explored. Methods Immunohistochemistry was performed in formalin‐fixed, paraffin‐embedded tissues of 87 serial brain biopsies sequentially obtained for diagnostic purposes in a period of 9 years (2000–2008) from an equal number of patients with low‐ and high‐grade gliomas. Results Higher expression of all proteins in high‐grade gliomas was documented. The univariate analysis revealed that high phospho‐p44/42( ERK 1/2) and high phospho‐ JNK expressions were strongly associated with decreased overall survival. However, the multivariate Cox regression failed to consider those markers as independent prognostic factors. Conclusion Activation of components of MAPK signaling pathway is associated with overall survival of patients with gliomas, thereby suggesting that the MAPK intermediates seem to play a critical role in the biologic behavior of gliomas. Further studies are needed to clarify whether these factors merit to be considered as potential therapeutic targets in future clinical trials.