AIMS: TP53 mutations are extremely rare in malignant pleural mesothelioma (MPM). In TP53 wild-type tumors, the functional p53 protein can be inactivated by MDM2. MATERIALS & METHODS: A total of 61 patient samples were tested for their Mdm2 and p53 protein expression levels via immunohistochemistry. RESULTS: This study demonstrates nuclear Mdm2 expression in three out of four mesothelioma cell lines and 21.3% of the MPM specimens investigated. After silencing of the MDM2 gene by siRNA in MPM cell lines, Mdm2 immunoexpression is lost and cells show changes indicative of severe damage. Mdm2 protein expression in MPM is detected in epithelioid and biphasic subtypes only and is significantly associated with poor survival compared with Mdm2-negative tumors. This may be explained by increased Mdm2 levels possibly leading to an increased ubiquitilation and proteasomal degradation of functional p53 protein. CONCLUSION: Expression of Mdm2 is a strong prognostic factor associated with shortened overall survival in MPM.
AIMS: TP53 mutations are extremely rare in malignant pleural mesothelioma (MPM). In TP53 wild-type tumors, the functional p53 protein can be inactivated by MDM2. MATERIALS & METHODS: A total of 61 patient samples were tested for their Mdm2 and p53 protein expression levels via immunohistochemistry. RESULTS: This study demonstrates nuclear Mdm2 expression in three out of four mesothelioma cell lines and 21.3% of the MPM specimens investigated. After silencing of the MDM2 gene by siRNA in MPM cell lines, Mdm2 immunoexpression is lost and cells show changes indicative of severe damage. Mdm2 protein expression in MPM is detected in epithelioid and biphasic subtypes only and is significantly associated with poor survival compared with Mdm2-negative tumors. This may be explained by increased Mdm2 levels possibly leading to an increased ubiquitilation and proteasomal degradation of functional p53 protein. CONCLUSION: Expression of Mdm2 is a strong prognostic factor associated with shortened overall survival in MPM.
Authors: Fabian Dominik Mairinger; Robert Werner; Elena Flom; Jan Schmeller; Sabrina Borchert; Michael Wessolly; Jeremias Wohlschlaeger; Thomas Hager; Thomas Mairinger; Jens Kollmeier; Daniel Christian Christoph; Kurt Werner Schmid; Robert Fred Henry Walter Journal: Virchows Arch Date: 2017-05-02 Impact factor: 4.064
Authors: R F H Walter; F D Mairinger; S Ting; C Vollbrecht; T Mairinger; D Theegarten; D C Christoph; K W Schmid; J Wohlschlaeger Journal: Br J Cancer Date: 2015-02-10 Impact factor: 7.640
Authors: Robert Fred Henry Walter; Claudia Vollbrecht; Robert Werner; Jeremias Wohlschlaeger; Daniel Christian Christoph; Kurt Werner Schmid; Fabian Dominik Mairinger Journal: Oncotarget Date: 2016-04-05
Authors: Fabian D Mairinger; Jan Schmeller; Sabrina Borchert; Michael Wessolly; Elena Mairinger; Jens Kollmeier; Thomas Hager; Thomas Mairinger; Daniel C Christoph; Robert F H Walter; Wilfried E E Eberhardt; Till Plönes; Jeremias Wohlschlaeger; Bharat Jasani; Kurt Werner Schmid; Agnes Bankfalvi Journal: Oncotarget Date: 2018-04-27
Authors: Robert F H Walter; Robert Werner; Michael Wessolly; Elena Mairinger; Sabrina Borchert; Jan Schmeller; Jens Kollmeier; Thomas Mairinger; Thomas Hager; Agnes Bankfalvi; Daniel C Christoph; Wilfried E E Eberhardt; Till Plönes; Clemens Aigner; Kurt W Schmid; Jeremias Wohlschlaeger; Fabian D Mairinger Journal: J Oncol Date: 2018-07-17 Impact factor: 4.375
Authors: Robert Fred Henry Walter; Claudia Vollbrecht; Robert Werner; Thomas Mairinger; Jan Schmeller; Elena Flom; Jeremias Wohlschlaeger; Nikolaos Barbetakis; Dimitrios Paliouras; Fotios Chatzinikolaou; Vasilis Adamidis; Kosmas Tsakiridis; Paul Zarogoulidis; Georgia Trakada; Daniel Christian Christoph; Kurt Werner Schmid; Fabian Dominik Mairinger Journal: J Cancer Date: 2016-09-13 Impact factor: 4.207