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PTEN expression is a strong predictor of survival in mesothelioma patients


Opitz, I; Soltermann, A; Abaecherli, M; Hinterberger, M; Probst-Hensch, N; Stahel, R; Moch, H; Weder, W (2008). PTEN expression is a strong predictor of survival in mesothelioma patients. European Journal of Cardio-Thoracic Surgery, 33(3):502-506.

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. 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.

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. 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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > University Hospital Zurich > Division of Surgical Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:09 Dec 2008 14:08
Last Modified:05 Apr 2016 12:38
Publisher:Elsevier
ISSN:1010-7940
Publisher DOI:https://doi.org/10.1016/j.ejcts.2007.09.045
PubMed ID:18248818

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