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.