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PTEN expression is a strong predictor of survival in mesothelioma patients

^a Division of Thoracic Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
^b Department of Pathology, Institute for Surgical Pathology, University Hospital Zurich, Zurich, Switzerland
^c Laboratory for Molecular Oncology, Clinic and Polyclinic of Oncology, University Hospital Zurich, Zurich, Switzerland
^d Molecular Epidemiology Unit/Cancer Registry Zurich, University Hospital Zurich, Zurich, Switzerland

Received 23 June 2007; received in revised form 18 September 2007; accepted 27 September 2007.

^_* Corresponding author. Tel.: +41 44 255 8802; fax: +41 44 255 8805. (Email: walter.weder{at}usz.ch).

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumour with poor prognosis and limited response to therapy. MPM is characterised by complex chromosomal aberrations, including chromosome 10 losses. The tumour suppressor gene phosphatase and tensin homologue deleted from chromosome 10 (PTEN) located on chromosome 10q23 plays an important role in different cancer, but its relevance for MPM is unclear. Patients and methods: In the present tissue microarray-based study, 341 MPM were studied for PTEN expression by immunohistochemistry using a monoclonal mouse PTEN antibody. Expression levels were semiquantitatively scored (negative, weak, moderate, strong). Expression of PTEN was correlated to overall survival. Results: Clinical data from 206 patients were available. One hundred and five patients were stage T4 and 92 patients presented with regional and mediastinal lymph node metastasis. Loss of PTEN expression was observed in 62% of the cases. The survival time was correlated to PTEN expression in 126 cases with complete follow-up data. Comparing any PTEN expression versus no expression, median survival time was significantly longer (log rank test p = 0.0001) in patients with PTEN expression (15.5 months; 95% CI: 3.8; 27.2 vs 9.7 months; 95% CI: 7.9; 11.7). Cox regression analysis revealed an association between PTEN expression and survival (p = 0.003) independently from the histological subtype (p = 0.7). Conclusion: PTEN is an independent prognostic biomarker in mesothelioma patients. The frequent loss of expression of the tumour suppressor gene PTEN suggests involvement of the PI3K-AKT/protein kinase B (PKB) pathway in MPMs, which may be relevant for future mesothelioma treatment.

Key Words: Malignant pleural mesothelioma • Tissue microarray • PTEN • Immunohistochemistry • Survival