Format

Send to

Choose Destination
Br J Cancer. 2015 Mar 3;112(5):883-90. doi: 10.1038/bjc.2015.27. Epub 2015 Feb 10.

MDM2 is an important prognostic and predictive factor for platin-pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A) seems to contribute to an MDM2-driven inactivation of P53.

Author information

1
1] Ruhrlandklinik, West German Lung Center, University Hospital Essen, University of Duisburg-Essen, Tüschener Weg 40, Essen D-45239, Germany [2] Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
2
Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
3
Institute of Pathology, University Hospital Cologne, Cologne, Germany.
4
Department of Pathology, Helios Klinikum Emil von Behring, Berlin, Germany.
5
1] Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany [2] Department of Medicine, Division of Medical Oncology, University of Colorado Denver, Aurora, CO, USA.

Abstract

BACKGROUND:

Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation.

METHODS:

A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS).

RESULTS:

OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P⩽0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival.

CONCLUSIONS:

MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.

PMID:
25668009
PMCID:
PMC4453955
DOI:
10.1038/bjc.2015.27
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center