Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

EGFR Overexpression In Malignant Pleural Mesothelioma. An Immunohistochemical And Molecular Study With Clinico-pathological Correlations.

A. Destro, G. Ceresoli, M. Falleni, P. Zucali, E. Morenghi, P. Bianchi, C. Pellegrini, N. Cordani, V. Vaira, M. Alloisio, A. Rizzi, S. Bosari, M. Roncalli
Published 2006 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
The epidermal growth factor receptor (EGFR) is overexpressed in many epithelial malignancies, against which some antitumoral drugs have been developed. There is a lack of information as to EGFR expression in malignant pleural mesothelioma (MPM), an aggressive and fatal cancer poorly responsive to current oncological treatments. Our aim was to: (a) compare EGFR immunohistochemical expression with mRNA levels measured by real time PCR; (b) assess the relationships between EGFR expression and clinico-pathological data including survival; (c) analyze the EGFR mutations. We developed an immunohistochemical method of EGFR evaluation based on the number of immunoreactive cells and staining intensity in 61 MPMs. EGFR immunoreactivity was documented in 34/61 (55.7%) cases. A significant correlation between EGFR protein and mRNA levels (p = 0.0077) was found, demonstrating the reliability of our quantification method of EGFR membrane expression. Radically resected patients (p = 0.005) and those with epithelial histotype (p = 0.048) showed an increased survival. No statistical correlation between EGFR immunoreactivity and patients survival was observed. No EGFR mutation was documented. This study documents EGFR overexpression in MPM at the protein and the transcriptional levels; it proposes a reliable method for EGFR expression evaluation in MPM. EGFR levels are not associated with clinico-pathological features of patients, including survival.
This paper references
10.1634/THEONCOLOGIST.7-SUPPL_4-31
Epidermal growth factor receptor dependence in human tumors: more than just expression?
C. Arteaga (2002)
10.1016/S1547-4127(04)00108-2
External beam radiation therapy for the treatment of pleural mesothelioma.
E. Baldini (2004)
10.1126/SCIENCE.1099314
EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy
J. Paez (2004)
10.1158/1078-0432.CCR-040010
Pemetrexed (ALIMTA), A Novel Multitargeted Antineoplastic Agent
A. Adjei (2004)
10.1056/NEJMOA040938
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.
T. Lynch (2004)
10.1038/modpathol.3800067
Diffuse malignant mesothelioma of the peritoneum and pleura, analysis of markers
J. Trupiano (2004)
10.1038/sj.bjc.6600299
Influence of epidermal growth factor receptor (EGFR), p53 and intrinsic MAP kinase pathway status of tumour cells on the antiproliferative effect of ZD1839 (‘Iressa’)
N. Magné (2002)
10.1200/JCO.2003.01.039
Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC.
F. Cappuzzo (2003)
10.1593/NEO.04271
Inhibition of proliferation, migration, and matrix metalloprotease production in malignant mesothelioma cells by tyrosine kinase inhibitors.
Z. Liu (2004)
10.1200/JCO.2004.22.90140.3007
Molecular correlates of the EGFR signaling pathway in association with SWOG S0218: a phase II study of oral EGFR tyrosine kinase inhibitor OSI-774 (NSC-718781) in patients with malignant pleural mesothelioma (MPM).
L. Garland (2004)
10.1158/1078-0432.CCR-04-1940
Gefitinib in Patients with Malignant Mesothelioma: A Phase II Study by the Cancer and Leukemia Group B
R. Govindan (2005)
10.1073/PNAS.0405220101
EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib.
W. Pao (2004)
10.1634/THEONCOLOGIST.8-6-576
Small-molecule epidermal growth factor receptor tyrosine kinase inhibitors.
M. Janmaat (2003)
10.1200/JCO.1992.10.5.686
Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features.
G. Gasparini (1992)
10.1043/1543-2165(2004)128<68:TGFAEG>2.0.CO;2
Transforming growth factor alpha and epidermal growth factor receptor in reactive and malignant mesothelial proliferations.
Yun-Cai Cai (2004)
10.1038/sj.bjc.6690105
The European mesothelioma epidemic
J. Peto (1999)
10.1200/JCO.2005.08.043
EGFR mutations in non-small-cell lung cancer: analysis of a large series of cases and development of a rapid and sensitive method for diagnostic screening with potential implications on pharmacologic treatment.
A. Marchetti (2005)
10.1200/JCO.2003.01.504
Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer.
J. Mendelsohn (2003)
10.1093/JNCI/DJH217
Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer.
F. Cappuzzo (2004)
10.1093/HMG/DDH331
Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839).
S. Kakiuchi (2004)
10.1093/ANNONC/MDH010
Activity of a specific inhibitor, gefitinib (Iressa, ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer.
A. Santoro (2004)
10.1186/gb-2002-3-7-research0034
Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes
J. Vandesompele (2001)
10.1007/978-3-642-60049-4_2
Histological Classification of Lung and Pleural Tumours
W. Travis (1999)
10.1016/J.JTCVS.2004.02.021
Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies.
D. Sugarbaker (2004)
Evaluation of dHPLC in mutation screening of the APC gene in a Greek FAP cohort.
M. Mihalatos (2003)
10.1016/S0022-5223(99)70469-1
Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients.
D. Sugarbaker (1999)
10.1007/BF00666180
The epidermal growth factor receptor as a prognostic marker: Results of 370 patients and review of 3009 patients
S. Fox (2004)
10.1038/bjc.1990.207
Malignant pleural mesothelioma and epidermal growth factor receptor (EGF-R). Relationship of EGF-R with histology and survival using fixed paraffin embedded tissue and the F4, monoclonal antibody.
H. Dazzi (1990)
10.1007/BF01626344
Immunohistochemical distribution patterns of epidermal growth factor receptor in malignant mesothelioma and non-neoplastic mesothelium
M. Ramael (2005)
10.1111/j.1365-2559.2004.01903.x
Testing for HER2 in breast cancer
Francis Lewis (2004)
10.1016/S0169-5002(01)00257-4
Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma.
G. Ceresoli (2001)
Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival.
J. Brabender (2001)
10.1038/sj.bjc.6601923
Analysis of epidermal growth factor receptor expression as a predictive factor for response to gefitinib (‘Iressa’, ZD1839) in non-small-cell lung cancer
H. Parrà (2004)
Inhibition of epidermal growth factor receptor signaling in malignant pleural mesothelioma.
P. Jänne (2002)
10.1200/JCO.2003.11.136
Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma.
N. Vogelzang (2003)
10.1007/978-3-642-60049-4
Histological Typing of Lung and Pleural Tumours
W. Travis (1999)
10.1016/S0140-6736(04)17108-0
Pleural mesothelioma: little evidence, still time to do trials
T. Treasure (2004)



This paper is referenced by
10.2217/14622416.9.8.1069
The serine protease HtrA1 is a novel prognostic factor for human mesothelioma.
A. Baldi (2008)
10.3892/or.2012.1725
Patients with peritoneal mesothelioma lack epidermal growth factor receptor tyrosine kinase mutations that would make them sensitive to tyrosine kinase inhibitors.
Neetu Kalra (2012)
10.2174/1874467210902020190
Malignant mesothelioma: biology, diagnosis and therapeutic approaches.
M. Tomasetti (2009)
10.1007/s00432-008-0444-9
Pathogenesis of malignant pleural mesothelioma and the role of environmental and genetic factors
Shoshana J. Weiner (2008)
10.1016/S0761-8425(07)78149-4
Prise en charge dignostique et thrapeutique du msothliome pleural malin en 2007
E. Porret (2007)
10.1093/carcin/bgp097
Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells.
K. Kawaguchi (2009)
10.1016/S1877-1203(09)72519-4
Traitements du mésothéliome pleural malin : le point en 2009
E. Bergot (2009)
10.1634/THEONCOLOGIST.12-7-850
Multidisciplinary treatment of malignant pleural mesothelioma.
G. Ceresoli (2007)
10.1016/S1470-2045(13)70139-6
Mesothelioma: closer to the target?
H. Pass (2013)
STUDIES ON SYNDECAN-1 IN MESENCHYMAL TUMORS
F. Zong (2010)
10.1371/journal.pone.0014110
Estrogen Receptor β Exerts Tumor Repressive Functions in Human Malignant Pleural Mesothelioma via EGFR Inactivation and Affects Response to Gefitinib
G. Pinton (2010)
10.1007/978-2-287-99041-0_20
Mésothéliome pleural malin
E. Bergot (2009)
10.1016/J.LUNGCAN.2007.08.035
Gene methylation in pleural mesothelioma: correlations with clinico-pathological features and patient's follow-up.
A. Destro (2008)
10.5858/arpa.2011-0215-RA
Molecular changes in mesothelioma with an impact on prognosis and treatment.
D. Jean (2012)
10.1080/15287394.2012.641203
Long-Term Response of Rats to Single Intratracheal Exposure of Libby Amphibole or Amosite
J. M. Cyphert (2012)
10.1007/s11864-011-0149-1
Novel Targeted Therapies and Vaccination Strategies for Mesothelioma
M. Bagia (2011)
10.1016/j.jtho.2016.05.020
The Genetic Landscape of Malignant Pleural Mesothelioma: Results from Massively Parallel Sequencing
Marieke Hylebos (2016)
10.1016/j.lungcan.2015.06.018
Second line therapy in malignant pleural mesothelioma: A systematic review.
W. Buikhuisen (2015)
10.1111/j.1743-7563.2007.00116.x
Management of malignant pleural mesothelioma
A. Nowak (2007)
10.1038/bjc.2011.400
Preclinical emergence of vandetanib as a potent antitumour agent in mesothelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin
E. Giovannetti (2011)
10.1007/s10147-011-0369-1
Pathological and molecular biological approaches to early mesothelioma
T. Tsujimura (2011)
10.1002/jso.21901
Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: Prognostic correlations
O. Rena (2011)
10.1038/bjc.2013.9
The expression of Axl receptor tyrosine kinase influences the tumour phenotype and clinical outcome of patients with malignant pleural mesothelioma
D. Pinato (2013)
10.1038/bjc.2015.286
Fibulin-3 levels in malignant pleural mesothelioma are associated with prognosis but not diagnosis
M. Kirschner (2015)
10.4137/BMI.S0
Expression of Cancer-Associated Molecules in Malignant Mesothelioma
B. Davidson (2007)
10.1016/j.lungcan.2010.01.002
Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma.
R. Gaafar (2010)
10.1111/j.1476-5381.2012.01873.x
Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma
R. Favoni (2012)
10.1038/bjc.2013.130
Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma
R. Mezzapelle (2013)
10.1016/j.mrgentox.2011.04.008
Crocidolite asbestos-induced signal pathway dysregulation in mesothelial cells.
H. Wang (2011)
10.1016/j.tips.2011.03.011
Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma.
R. Favoni (2011)
10.1097/JTO.0b013e31819c8661
Absence of mutations in the epidermal growth factor receptor (EGFR) kinase domain in patients with mesothelioma.
V. Velcheti (2009)
10.1080/13543784.2017.1351545
Promising investigational drug candidates in phase I and phase II clinical trials for mesothelioma
A. Guazzelli (2017)
See more
Semantic Scholar Logo Some data provided by SemanticScholar