Putative biomarkers in malignant pleural mesothelioma.

Abstract

e21008 Background: Malignant pleural mesothelioma (MPM) is associated with chronic inflammation due to asbestos exposure. The expression of inflammatory biomarkers associated with oncogenesis, e.g. cyclooxygenase-2 (COX2), 5-Lipoxygenase (5-LOX) and 12-LOX, may be of clinical relevance in MPM. In addition the PTEN/PI3K/AKT/MTOR signal transduction pathway may be aberrant in MPM. Loss of PTEN expression may lead to constitutive activation of AKT, resulting in cell survival and proliferation. In this study we aimed to assess the clinical relevance of 5-LOX, 12-LOX and PTEN protein expression in a large series of MPM samples. Methods: Immunohistochemical analysis was performed in 93 archival MPM tissue samples (48 epithelial, 27 biphasic, 18 sarcomatoid) to determine the expression of the PTEN, 5-LOX and 12-LOX proteins. Survival data were available for all 93 patients and prognostic factors were assessed using univariate and multivariate analyses. Results: Positive 5-LOX expression was seen in 73% (65/88) of samples and this was associated with improved survival (median overall survival 8.3 months versus 4.6 months; p=0.006). However, when histological subtype was taken into consideration, multivariate Cox regression analysis demonstrated that 5-LOX expression was not an independent prognostic variable (p=0.074). Positive 12-LOX expression was seen in 83% (69/83) of samples, but this was not associated with survival (p=0.455). Correlating this LOX expression data with our previously published COX2 expression results in the same cohort (Eur J Cancer 41:1645-8; 2005) revealed significant correlations. Positive 5-LOX expression correlated with positive COX2 expression (p=0.002). Positive 12-LOX expression correlated with 5-LOX co-expression (p=0.006). The expression of PTEN was lost in 27% (23/86) of samples and this was not associated with survival (p=0.223). Conclusions: We have demonstrated that 5-LOX and 12-LOX are expressed in a significant proportion of MPM samples and therefore may be novel therapeutic targets. Loss of PTEN expression was seen in 27% of samples. This research may lead to novel therapeutic strategies for patients with MPM.