title: PTEN expression is a strong predictor of survival in mesothelioma patients.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Opitz
authors.forename: Alex
authors.initials: A
authors.lastname: Soltermann
authors.forename: Martin
authors.initials: M
authors.lastname: Abaecherli
authors.forename: Marc
authors.initials: M
authors.lastname: Hinterberger
authors.forename: Nicole
authors.initials: N
authors.lastname: Probst-Hensch
authors.forename: Rolf
authors.initials: R
authors.lastname: Stahel
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Walter
authors.initials: W
authors.lastname: Weder
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D051379:Mice; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human