RT Journal Article
SR Electronic
T1 E3 ubiquitin-protein ligase (mouse double minute 2; Mdm2) protein expression is strongly associated with poor overall survival in malignant pleural mesothelioma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P543
VO 42
IS Suppl 57
A1 Fabian Mairinger
A1 Saskia Ting
A1 Claudia Vollbrecht
A1 Robert Walter
A1 Jens Kollmeier
A1 Sergej Grief
A1 Thomas Hager
A1 Thomas Mairinger
A1 Daniel Christoph
A1 Kurt Werner Schmid
A1 Jeremias Wohlschlaeger
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P543.abstract
AB Background: Malignant Pleural Mesothelioma (MPM) is a biologically aggressive tumour leading to a dismal prognosis, for which novel and/or additional treatment modalities are needed. In contrast to other solid malignancies, TP53 mutations are extremely rare in MPM. However, in TP53 wild-type tumours, the function of P53 can be deleted by the E3 ubiquitin protein ligase homolog (Mdm2), which is overexpressed in several tumour types including lung carcinomas.Material and methods: The protein expression of P53 and Mdm2 was assessed in five different mesothelioma cell lines by immunocytochemsitry. Moreover, Mdm2 and P53 expression was investigated by immunohistochemistry in tissue microarrays (TMA) from 61 patients with MPM of varying subtypes and survival analyses were performed.Results: In three out of five mesothelioma cell lines, nuclear reactivity for Mdm2 was demonstrated. 13 out of 61 (21.3%) MPM tissue specimens showed nuclear expression of Mdm2. Mdm2 protein expression was observed in epithelioid MPM only and in epithelioid parts of biphasic MPM. Expression of the P53 protein could not be detected. Statistical analysis of the Cox-regression showed a significant association between Mdm2 expression and survival in a linear (p=0.0242) and logarithmic scale (p=0.0226).Conclusions: Mdm2 protein expression was detected in epithelioid MPM only, and is significantly associated with poor survival in MPM of epithelioid and biphasic subtypes compared to Mdm2 negative tumours, leading to ubiquitination and proteasomal degradation of functional P53 protein.