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PTEN protein expression in malignant pleural mesothelioma

Agarwal, Vijay; Campbell, Anne; Beaumont, Kate L.; Cawkwell, Lynn; Lind, Michael J.

Authors

Vijay Agarwal

Anne Campbell

Kate L. Beaumont

Professor Michael Lind M.J.Lind@hull.ac.uk
Foundation Professor of Oncology/ Head of the Joint Centre for Cancer Studies

Abstract

Malignant pleural mesothelioma is associated with poor prognosis and despite recent advances in chemotherapy, the median survival is still approximately 12 months. Loss of phosphatase and tensin homolog (PTEN) protein expression may lead to constitutive activation of AKT resulting in cell survival and proliferation. Small studies reported that PTEN protein expression is rarely lost in mesothelioma whilst a larger study demonstrated prognostic significance of PTEN protein expression status with absence in 62 % of cases. We aimed to analyse PTEN protein expression in mesothelioma. Immunohistochemical analysis was performed in 86 archival mesothelioma samples to determine the PTEN protein expression status and statistical analysis was performed to identify any prognostic significance. Mesothelial cells in normal pleura demonstrated positive staining for PTEN protein and served as a positive reference. For mesothelioma samples, the expression of PTEN protein was scored as 0 (negative), 1 (intensity less than that of positive normal pleura reference slide) and 2 (intensity equal to or greater than positive normal pleura reference slide). A total of 23/86 (26.7 %) scored 0, 23/86 (26.7 %) scored 1 and 40/86 (46.5 %) scored 2 for PTEN expression. Univariate analysis demonstrated that lack of PTEN expression was not associated with survival. PTEN protein expression was undetectable in 26.7 % of mesothelioma samples; however, no prognostic significance was identified. Absence of PTEN protein may result in activation of the PI3K/AKT/MTOR pathway. Targeting this pathway with inhibitors further downstream of PTEN may provide a potential therapeutic target in selected patients.

Journal Article Type Article
Publication Date Apr 1, 2013
Journal Tumor Biology
Print ISSN 1010-4283
Electronic ISSN 1423-0380
Publisher SAGE Publications
Peer Reviewed Peer Reviewed
Volume 34
Issue 2
Pages 847-851
Institution Citation Agarwal, V., Campbell, A., Beaumont, K. L., Cawkwell, L., & Lind, M. J. (2013). PTEN protein expression in malignant pleural mesothelioma. Tumor Biology, 34(2), 847-851. doi:10.1007/s13277-012-0615-9
DOI https://doi.org/10.1007/s13277-012-0615-9
Keywords AKT; Immunohistochemistry; Mesothelioma; MTOR pathway; PTEN
Publisher URL https://link.springer.com/article/10.1007%2Fs13277-012-0615-9