title: Phosphorylated extracellular signal-regulated kinases are significantly increased in malignant mesothelioma.
abstract: Tumorigenesis is associated with the activation of mitogenic signal transduction pathways. The expression of activated extracellular signal-regulated kinase (p-ERK) may play an important role in cell proliferation of malignant mesothelioma (MM). We compare the expression of p-ERK in 50 biopsy specimens of MM, non-small-cell lung cancer (NSCLC), and normal lung tissue. We hypothesized that phosphorylated extracellular signal-regulated kinase is increased in MM. We stained the sections by immunohistochemistry for activated ERK-1 and -2 and performed the quantification of the stained nuclei. Quantitative analysis of p-ERK showed a high percentage score in MM (30.3 +/- 4.6%) as compared with NSCLC (12.2 +/- 2.1%) (p<0.01) and control lung tissue (6.4 +/- 1.3%) (p=0.0002). Furthermore, p-ERK was found significantly higher in poorly differentiated NSCLC (17.7 +/- 3.1%) as compared with well-differentiated NSCLC (5.4 +/- 1.2%) (p<0.01). Our data show that the nuclear quantification of p-ERK is significantly increased in MM and poorly differentiated NSCLC in comparison to well-differentiated NSCLC and normal lung tissue. These results corroborate previous experimental studies that suggest a critical role of p-ERK in cell proliferation of malignant disease and may represent new targets for therapeutic agents.
authors.affiliation: Division of Clinical Pathology, Centre Medical Universitaire (CMU), 1 Rue Michel-Servet, 1211 Geneva 4, Switzerland.
authors.forename: Merivane
authors.initials: M
authors.lastname: de Melo
authors.forename: Margaret W
authors.initials: MW
authors.lastname: Gerbase
authors.forename: Joseph
authors.initials: J
authors.lastname: Curran
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pache
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology*; D008175:Lung Neoplasms / Q000201:enzymology*; D008654:Mesothelioma / Q000201:enzymology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3