Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations

Our plain-English summary of Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations, by O. Rena, L.R. Boldorini, E. Gaudino, et al (Journal of Surgical Oncology, 2011).

The study

• Authors: O. Rena, L.R. Boldorini, E. Gaudino, C. Casadio
• Journal: Journal of Surgical Oncology
• Published: 2011;104(6):701-5
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: To evaluate epidermal growth factor receptor (EGFR) phenotypic expression and related gene status in malignant pleural mesothelioma (MPM) and to correlate the results with patients' prognosis.

Method: Eighty-three cases of MPM specimens were submitted to immunohistochemical (IHC) staining to evaluate the expression of EGFR protein; positive cases were submitted to fluorescence in situ hybridization (FISH) to investigate the gene status. Results were correlated with clinico-pathological characteristics and long-term survival.

Results: Thirty-eight cases (46%) demonstrated a positive IHC reaction [30/57 (52%) epithelial and 8/20 (40%) biphasic whereas sarcomatous MPM were negative]. No association was recorded between EGFR IHC positive staining and age, gender, or asbestos exposure. Three out of 38 (8%) cases submitted to FISH were positive revealing gene amplification or polysomy. Mean follow-up was 15.4 months (range 2-44). Epithelial subtype only was confirmed to affect prognosis (2-years survival rate 40 vs. 18% for non-epithelial subtype, P = 0.042). When epithelial MPM patients were considered, IHC EGFR positive staining was demonstrated to be a negative prognostic factor (2-years survival rate 26 vs. 60% for IHC EGFR negative staining; P = 0.026).

Conclusions: EGFR overexpression is identified by IHC in 52% of epithelial MPM and is demonstrated to be a factor negatively affecting prognosis. Phenotypic overexpression seems not to be related to gene status alteration.

Copyright © 2011 Wiley Periodicals, Inc.

In plain English

This study, from a thoracic surgery unit in Novara, Italy, examined tumor tissue from 83 patients with malignant pleural mesothelioma. The samples were obtained between January 2005 and August 2008, and 68% of the patients had a history of asbestos exposure. The authors stained the samples for a protein called epidermal growth factor receptor (EGFR) and counted the strongest-staining cases (score 3+) as positive. Of the 83 cases, 38 (46%) were positive: 30 of 57 epithelial, 8 of 20 biphasic and none of 6 sarcomatous tumors. EGFR staining showed no statistical association with age, gender or asbestos exposure. Gene testing of the 38 positive cases found a copy number gain in 3. Survival data were available for 67 patients. Across all patients, EGFR status was not significantly linked to survival (2-year survival 45% for negative versus 22% for positive, P = 0.087). Among patients with epithelial tumors, 2-year survival was 26% with EGFR-positive tumors versus 60% with EGFR-negative tumors (P = 0.026). The authors concluded that EGFR positivity could be a negative prognostic factor in epithelial mesothelioma and called for larger studies.

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: Laboratory study of stored tumor tissue (immunohistochemical staining and FISH gene testing), with results compared against patients' clinical features and survival
• Who was studied: 83 patients with malignant pleural mesothelioma whose tumor samples were obtained by surgery or biopsy between January 2005 and August 2008 at the Thoracic Surgery Unit of the University of Eastern Piedmont, Novara, Italy. 58 (70%) were male, mean age was 67, and there were 57 epithelial, 20 biphasic and 6 sarcomatous tumors.
• Exposure: Asbestos exposure was recorded for 56 patients (68%). Fiber types and exposure levels were not reported. The factor studied was EGFR protein expression and EGFR gene status in the tumor.
• Main results:
  • EGFR staining was found in 70/83 (84%) cases. 38/83 (46%) scored 3+ and were considered positive.
  • EGFR-positive staining by subtype: 30/57 (52%) epithelial, 8/20 (40%) biphasic and 0/6 sarcomatous tumors.
  • No statistical association was found between EGFR expression and gender, age or asbestos exposure.
  • Of the 38 positive cases tested by FISH, 3 showed an EGFR gene copy number gain (1 high polysomy, 2 gene amplification). All 3 were epithelial subtype.
  • Follow-up data were available for 67/83 patients, with a mean follow-up of 15.4 months (range 2 to 44).
  • 2-year survival was 40% for epithelial versus 18% for non-epithelial mesothelioma (P = 0.042).
  • In the whole patient group, EGFR staining did not significantly influence overall survival: 2-year survival was 45% for EGFR-negative versus 22% for EGFR-positive (P = 0.087).
  • Among epithelial mesothelioma patients, 2-year survival was 26% for EGFR-positive versus 60% for EGFR-negative staining (P = 0.026).
  • When epithelial and biphasic tumors were considered together, 2-year survival was 22% for EGFR-positive versus 52% for EGFR-negative staining (P = 0.029).
  • In multivariate analysis, epithelial subtype and EGFR-positive (3+) staining within the epithelial subtype were reported as independent variables affecting long-term prognosis.
• The authors' conclusion: The authors concluded that EGFR overexpression is common in malignant pleural mesothelioma, especially the epithelial subtype. They concluded that EGFR-positive staining could be a negative prognostic factor in epithelial mesothelioma, and that the protein overexpression was not related to gene amplification. They suggested that a subgroup of patients might benefit from anti-EGFR therapy, and said larger studies were needed to confirm this.
• Limitations the authors state:
  • The prognostic impact of EGFR gene amplification could not be analyzed statistically because only 3 patients had a positive FISH result.
  • The authors stated that further and larger studies are needed to confirm their findings.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, EGFR, Prognosis, Fluorescence In Situ Hybridization (FISH), Biphasic Mesothelioma, Asbestos Exposure.

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