EGFR expression: associations with outcome and clinicopathological variables in malignant pleural mesothelioma

Our plain-English summary of EGFR expression: associations with outcome and clinicopathological variables in malignant pleural mesothelioma, by J.G. Edwards, D.E. Swinson, J.L. Jones, et al (Lung Cancer, 2006).

The study

• Authors: J.G. Edwards, D.E. Swinson, J.L. Jones, D.A. Waller, K.J. O'Byrne
• Journal: Lung Cancer
• Published: 2006;54(3):399-407
• Cited by: 65 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant mesothelioma (MM) is a fatal tumour of increasing incidence which is related to asbestos exposure. This work evaluated expression in MM of Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry in 168 tumour sections and its correlations with clinicopathological and biological factors. The microvessel density (MVD) was derived from CD34 immunostained sections. Hematoxylin and eosin stained sections were examined for intratumoural necrosis. COX-2 protein expression was evaluated with semi-quantitative Western blotting of homogenised tumour supernatants (n=45). EGFR expression was correlated with survival by Kaplan-Meier and log rank analysis. Univariate and multivariate Cox proportional hazards models were used to compare the effects of EGFR with clinicopathological and biological prognostic factors and prognostic scoring systems. EGFR expression was identified in 74 cases (44%) and correlated with epithelioid cell type (p<0.0001), good performance status (p<0.0001), the absence of chest pain (p<0.0001) and the presence of TN (p=0.004), but not MVD or COX-2. EGFR expression was a good prognostic factor in univariate analysis (p=0.01). Independent indicators of poor prognosis in multivariate analysis were non-epithelioid cell type (p=0.0001), weight loss, performance status and WBC>8.3x10(9)L(-1). EGFR status was not an independent prognostic factor. EGFR expression in MM correlates with epithelioid histology and TN. EGFR may be a target for selective therapies in MM.

In plain English

The authors stained tumour samples from 168 patients with malignant mesothelioma, seen at their institution since 1988, for a protein called EGFR (epidermal growth factor receptor). EGFR was found in 74 of the 168 tumours (44%). EGFR-positive tumours were more often of the epithelioid cell type. They came more often from patients without chest pain and with better performance status (a measure of daily functioning), and more often contained dead tumour tissue (necrosis). EGFR was not linked to tumour blood-vessel density, COX-2 levels or recorded asbestos exposure. The survival analysis left out 18 patients who died of surgical complications within 30 days. Among the rest, median survival was 270 days for the 69 EGFR-positive patients and 170 days for the 81 EGFR-negative patients. Once cell type, weight loss and performance status were taken into account, EGFR was not an independent predictor of survival. Among epithelioid tumours alone it made no significant difference. The authors concluded that the better survival seen with EGFR may be due to its link with other signs of good prognosis, such as cell type.

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: Retrospective study of archived tumour samples and case notes, using immunohistochemical staining for EGFR and survival analysis
• Who was studied: 168 patients with malignant mesothelioma diagnosed by tissue biopsy and presenting to the authors' institution (affiliated with Leicester, UK) since 1988. 151 were male and 17 female. Survival analyses used 150 patients, after excluding 18 who died of surgical complications within 30 days.
• Exposure: The factor studied was EGFR expression in the tumour, not asbestos. Asbestos exposure was recorded only as yes or no, with no fiber types or doses. Among patients with this information, 115 were recorded as exposed and 26 as not exposed.
• Main results:
  • EGFR staining was present in 74 of 168 tumours (44%): membranous only in 10, cytoplasmic only in 28, and both in 36.
  • EGFR staining was associated with absence of chest pain (p less than 0.0001), epithelioid cell type (p less than 0.0001) and ECOG performance status 0 (p less than 0.0001).
  • EGFR-positive tumours more often showed tumour necrosis (p = 0.004).
  • EGFR status was not correlated with microvessel density (measured in 128 cases).
  • EGFR status was not correlated with COX-2 protein levels (measured in 45 tumours).
  • EGFR status was not associated with recorded asbestos exposure: EGFR-positive in 53 of 115 exposed and 12 of 26 non-exposed patients (p = 0.99).
  • Excluding 18 early postoperative deaths, median survival was 170 days for the 81 EGFR-negative cases and 270 days for the 69 EGFR-positive cases (p = 0.0125, log rank).
  • In univariate analysis, absence of EGFR expression gave a hazard ratio of 1.5 (95% CI 1.1 to 2.1, p = 0.013).
  • In multivariate analysis, EGFR status was not an independent prognostic factor (p = 0.95 in the first model). The independent predictors of poor survival were non-epithelioid cell type (hazard ratio 2.56, 95% CI 1.77 to 3.71), weight loss over 5% (hazard ratio 1.73) and ECOG performance status above 0 (hazard ratio 1.58).
  • Among the 88 epithelioid cases alone, survival did not differ significantly between EGFR-positive and EGFR-negative cases (p = 0.74).
• The authors' conclusion: The authors concluded that EGFR expression is common in mesothelioma. They wrote that although it was associated with a favourable prognosis, this may be due to its relationship with other indicators of good prognosis such as cell type, and that EGFR was not an independent prognostic factor. They suggested EGFR may still be a target for selective therapies.
• Limitations the authors state:
  • Separate multivariate analyses for epithelioid and non-epithelioid cases were not done because the numbers were small.
  • COX-2 was not entered into multivariate analysis because the numbers were small.
  • It is unknown whether the antibody used detects variant EGFR proteins caused by EGFR gene alterations reported in some mesotheliomas.

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, Malignant Mesothelioma, Asbestos Exposure, Immunohistochemistry, CD34, Necrosis, Epithelioid.

Related studies

• Tissue and serum EGFR as prognostic factors in malignant pleural mesothelioma — R. Gaafar, A. Bahnassy, et al. (2010)
• EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors — H. Kothmaier, F. Quehenberger, et al. (2008)
• Tumor necrosis correlates with angiogenesis and is a predictor of poor prognosis in malignant mesothelioma — J.G. Edwards, D.E. Swinson, et al. (2003)
• EGFR Status in Mesothelioma: Possible Implications for the Efficacy of Anti-EGFR and Anti-MET Therapies — S. Salvi, S. Varesano, et al. (2016)
• A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma — Y. Enomoto, T. Kasai, et al. (2012)
• Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells — K. Kawaguchi, H. Murakami, et al. (2009)

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