Phosphorylated Extracellular Signal-regulated Kinases are Significantly Increased in Malignant Mesothelioma

Journal of Histochemistry & Cytochemistry. 2006 Mar 3; [Epub ahead of print] [Link]

Merivane de Melo 1, Margaret W. Gerbase 1, Joseph Curran 1 and Jean-Claude Pache 1*

1 Divisions of Clinical Pathology (MdM,J-CP) and Pulmonary Medicine (MWG), University Hospital of Geneva, Geneva, Switzerland, and Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland (JC)

* To whom correspondence should be addressed. E-mail:


Tumorigenesis is associated with the activation of mitogenic signal transduction pathways. The expression of activated extracellular signal regulated kinase (pERK) may play an important role in cell proliferation of malignant mesothelioma. We compare the expression of pERK in 50 biopsy specimens of malignant mesothelioma (MM), non small cell lung cancer (NSCLC), and normal lung tissue. Here, we hypothesized that phosphorylated extracellular signal regulated kinase is increased in mesothelioma. We stained the sections by immunohistochemistry for activated ERK-1 and 2 and performed the quantification of the stained nuclei. Quantitative analysis of pERK showed a high percentage score in malignant mesothelioma (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, pERK 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 pERK 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 pERK in cell proliferation of malignant disease and may represent new targets for therapeutic agents.

Keywords: human malignant mesothelioma, non small cell lung carcinoma, ERK1/2, PI3K/AKT