title: Extracellular signal-regulated kinase (ERK) expression and activation in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival.
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.
authors.affiliation: Department of Pathology, Institut Curie, Paris, France, statheocharis@yahoo.com.
authors.forename: Stamatios
authors.initials: S
authors.lastname: Theocharis
authors.forename: Ioly
authors.initials: I
authors.lastname: Kotta-Loizou
authors.forename: Jerzy
authors.initials: J
authors.lastname: Klijanienko
authors.forename: Constantinos
authors.initials: C
authors.lastname: Giaginis
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Alexandrou
authors.forename: Eougken
authors.initials: E
authors.lastname: Dana
authors.forename: Jose
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D014062:Tongue Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3