Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma

Our plain-English summary of Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma, by R. Gaafar, A. Bahnassy, I. Abdelsalam, et al (Lung Cancer, 2010).

The study

• Authors: R. Gaafar, A. Bahnassy, I. Abdelsalam, M.M. Kamel, A. Helal, A. Abdel-Hamid, N.A. Eldin, N. Mokhtar
• Journal: Lung Cancer
• Published: 2010;70(1):43-50
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Malignant pleural mesothelioma (MPM) is an asbestos related aggressive tumor. Asbestos causes genetic modifications and cell signaling events that favor resistance to chemotherapy. A variety of receptor tyrosine kinases have been identified to play a central role in various aspects of tumorigenesis. Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer in which EGFR aberrations not only predict response to EGFR tyrosine kinase inhibitors but also indicate tumor progression. However in MPM, the role of EGFR is less clear. This study was designed to identify serum and tissue EGFR levels in patients with MPM and to evaluate the relationship between serum and tissue EGFR levels and clinicao-pathological prognostic factors and survival.

Methods: We investigated 71 cases of MPM for EGFR expression in tissue. Serum EGFR was assessed in 40 out of those 71 cases and 20 healthy subjects as a control. Pre-treatment serum EGFR levels were measured using quantitative enzyme-linked immunosorbent assay. Tissue EGFR protein overexpression was assessed by immunohistochemistry and gene amplification was assessed by the chromogen in situ hybridization (CISH) technique. Results were correlated with the clinical-pathological factors of the patients and overall survival (OS).

Results: Out of the 71 patients included in the study, 19 had undergone extrapleural pneumonectomy. As for the rest of the patients, 46 received chemotherapy while 6 had only best supportive care. EGFR immuno-reactivity was detected in 74.6% of the cases, 37 (52.1%) cases were positive for EGFR gene amplification by CISH, 31 of them revealed moderate to high (++, +++) EGFR immuno-reactivity. Elevated serum EGFR >2.5 ng/ml (the median concentration of EGFR in MPM) was reported in 45% of the cases. The overall response rate (RR) for the 46 treated patients who received chemotherapy was 24.1%. After a median follow up of 29 months, the median overall survival (OS) was 10 months. Elevated serum and tissue EGFR is significantly associated with advanced disease stage. However neither EGFR overexpression in tissues nor high serum levels were associated with survival rates.

Conclusions: EGFR expression is a common feature in MPM patients. High pre-treatment levels of serum EGFR are associated with advanced stage but not with reduced OS. Detailed mutational analysis of EGFR on a larger number of patients is still needed to clarify the exact role of EGFR in MPM patients.

Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

In plain English

This prospective study at the National Cancer Institute, Cairo University, Egypt, measured a protein called EGFR (epidermal growth factor receptor) in 71 malignant pleural mesothelioma patients seen from 2004 to 2007. The authors tested tumor tissue from all 71, blood serum from 40 of them, and serum from 20 healthy volunteers. Fifty of the 71 patients gave a history of asbestos exposure. The article did not report fiber types. Median serum EGFR was 2.5 ng/ml in patients and 0.23 ng/ml in healthy controls (p = 0.001). EGFR was detected in tumor tissue from 53 of 71 patients (74.6%), and the EGFR gene was amplified in 37 (52.1%). High serum EGFR was associated with advanced disease stage. Neither serum nor tissue EGFR was significantly related to asbestos exposure history or overall survival. For example, median survival was 6 months (95% CI 2 to 10) with serum EGFR above 2.5 ng/ml versus 8 months (95% CI 5 to 11) at or below it (p = 0.44). The authors concluded that EGFR expression is common but not associated with reduced survival, and that larger studies are needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: prospective study of tumor tissue and serum markers, with survival analysis
• Who was studied: 71 patients with malignant pleural mesothelioma at the National Cancer Institute, Cairo University, Egypt, 2004 to 2007. Pre-treatment serum was available for 40 of them, and serum from 20 healthy volunteers served as controls.
• Exposure: The study measured EGFR in tissue and serum, not asbestos dose. A history of asbestos exposure was recorded in 50 of 71 patients (70.4%). Fiber types were not reported.
• Main results:
  • Median serum EGFR was 2.5 ng/ml in mesothelioma patients versus 0.23 ng/ml in healthy controls (p = 0.001)
  • 18 of the 40 patients with serum samples (45%) had serum EGFR above 2.5 ng/ml
  • High serum EGFR was associated with advanced disease stage (p = 0.05), and serum EGFR level was associated with T-stage (p = 0.001)
  • EGFR was detected in tumor tissue by immunostaining in 53 of 71 cases (74.6%)
  • EGFR gene amplification was found in 37 of 71 cases (52.1%)
  • Tissue EGFR overexpression and gene amplification were associated with T-stage (p = 0.021)
  • EGFR in serum and in tissue was not significantly related to history of asbestos exposure (p = 0.56 and p = 0.78 respectively)
  • Median survival was 6 months (95% CI 2 to 10) for patients with serum EGFR above 2.5 ng/ml and 8 months (95% CI 5 to 11) for those at or below 2.5 ng/ml (p = 0.44)
  • Median survival was 12 months (95% CI 9 to 15) for patients with EGFR-positive tumors versus 8 months (95% CI 3 to 13) for patients with EGFR-negative tumors (p = 0.27)
  • Median survival was 10 months (95% CI 8 to 16) with EGFR gene amplification versus 7 months (95% CI 5 to 13) without it (p = 0.26 in the text)
  • Among the 46 advanced-stage patients given chemotherapy, the overall response rate was 24%
• The authors' conclusion: The authors concluded that EGFR expression is common in these mesothelioma patients and that high pre-treatment serum EGFR is associated with advanced stage but not with reduced overall survival.
• Limitations the authors state:
  • The authors said a detailed mutational analysis of EGFR in a larger number of patients is still needed to clarify its role.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: EGFR, Pleural Mesothelioma, Chemotherapy, Tumorigenesis, Lung Cancer, Tyrosine Kinase Inhibitor, Immunohistochemistry, Overall Survival.

Related studies

• EGFR expression: associations with outcome and clinicopathological variables in malignant pleural mesothelioma — J.G. Edwards, D.E. Swinson, et al. (2006)
• Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations — O. Rena, L.R. Boldorini, et al. (2011)
• EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors — H. Kothmaier, F. Quehenberger, et al. (2008)
• Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma: A meta-analysis — Y. Zhuo, L. Lin, et al. (2016)
• Mesothelin-related predictive and prognostic factors in malignant mesothelioma: a nested case-control study — O.D. Roe, J. Creaney, et al. (2008)
• 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, P.S. Hasleton, et al. (1990)

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