Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma

Our plain-English summary of Epidermal growth factor receptor mutations in malignant pleural and peritoneal mesothelioma, by Y. Enomoto, T. Kasai, M. Takeda, et al (Journal of Clinical Pathology, 2012).

The study

• Authors: Y. Enomoto, T. Kasai, M. Takeda, M. Takano, K. Morita, E. Kadota, N. Iizuka, H. Maruyama, J. Haratake, Y. Kojima, N. Ikeda, N. Inatsugi, A. Nonomura
• Journal: Journal of Clinical Pathology
• Published: 2012;65(6):522-7
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Epidermal growth factor receptor (EGFR) gene mutation at the kinase domain and EGFR gene amplification are reported to be predictors of the response to EGFR tyrosine kinase inhibitors in lung cancer cases. In malignant mesothelioma (MM), the role of EGFR is less clear.

Methods: Thirty-eight MM specimens were submitted to EGFR mutation evaluation, and compared with the results of immunohistochemical staining and fluorescence in situ hybridization (FISH) analysis. DNA was extracted from paraffin blocks and PCR was performed to amplify exon regions 18-21 of the EGFR gene. Direct sequencing of the purified PCR products was performed.

Results: Five EGFR missense mutations were detected in six of the 38 patients (16%); two of these mutations were novel, two were originally detected in non-small cell lung carcinoma, and one resembled a location previously noted for malignant peritoneal mesothelioma.

Conclusion: As far as the authors are aware there has been no report of the EGFR mutation of MM in Japanese cases, but in this study EGFR missense mutations were detected in some cases. EGFR mutation results were not related to immunohistochemical and FISH analysis.

In plain English

This laboratory study from Japan examined archived tumour tissue from 38 people with malignant mesothelioma (22 pleural, 16 peritoneal). The tissue came from a university pathology department and five hospitals. The authors looked for mutations in the EGFR gene, whose mutations can predict response to certain targeted drugs in lung cancer. They compared the results with EGFR protein staining and with counts of EGFR gene copies. Strong (3+) EGFR staining was found in 20 of 38 tumours (53%). It was more common in the epithelioid subtype than in other subtypes (67% vs 21%, p less than 0.01). Only one tumour showed an EGFR gene copy number gain. EGFR mutations were found in 6 of the 38 patients (16%), and one patient had two. The authors called two of the mutation types novel. They described the difference in mutation frequency between peritoneal and pleural cases (19% vs 14%) as negligible. Mutations were not related to the staining or copy number results. The article did not report patients' asbestos exposure. The authors concluded that EGFR overexpression is common in mesothelioma 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: Laboratory (pathology) study of archived tumour specimens, testing for EGFR gene mutations by DNA sequencing and comparing the results with EGFR protein staining (immunohistochemistry) and gene copy number (FISH)
• Who was studied: 38 Japanese cases of malignant mesothelioma (22 pleural, 16 peritoneal), median age 63 years, range 41 to 81. Histologic subtypes: 25 epithelioid, 7 biphasic and 6 sarcomatoid. Cases were collected from the archives of Nara Medical University's pathology department and five hospitals. Ten benign mesothelial lesions and five pleuritis cases were also examined, but no results are reported for them.
• Exposure: Not studied. The article did not report asbestos or other exposure for these patients. It examined the EGFR gene and EGFR protein in tumour tissue.
• Main results:
  • EGFR missense mutations were detected in 6 of the 38 patients (16%).
  • One patient (case 28) had two mutations, one in exon 20 and one in exon 21.
  • Of the five mutation types found, the authors reported two as novel and two as originally detected in non-small cell lung cancer. One resembled a location previously noted for malignant peritoneal mesothelioma.
  • Mutation frequency was 19% in peritoneal and 14% in pleural mesothelioma. The authors described this difference as negligible.
  • No associations were confirmed between EGFR mutation and other factors.
  • Strong (3+, counted as positive) EGFR protein staining was found in 20 of 38 cases (53%). Some EGFR staining was seen in 37 of 38 cases (97%).
  • Positive EGFR staining was seen in 11 of 22 (50%) pleural and 9 of 16 (56%) peritoneal mesotheliomas.
  • Positive EGFR staining was more common in epithelioid than in non-epithelioid cases (67% vs 21%), a statistically significant difference (p less than 0.01).
  • Only 1 of 38 cases showed an EGFR gene copy number gain (high polysomy). No significant correlation was shown between EGFR protein expression and gene amplification.
  • The mutation results were repeated using DNA from a second paraffin block of the same tumour, giving identical results.
• The authors' conclusion: The authors concluded that EGFR overexpression is a common feature of malignant mesothelioma, especially the epithelial subtype, and that it was not related to gene copy number gain. They said larger studies are needed to select mesothelioma patients for anti-EGFR therapy. They also stated that EGFR mutation was not related to the staining and FISH results.
• Limitations the authors state:
  • The authors stated that further and larger studies are needed to select candidates for anti-EGFR therapy.
  • The study did not examine whether EGFR expression is linked to prognosis (survival). The authors said they will examine this in the future.

Topics

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

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, EGFR, Tyrosine Kinase Inhibitor, Lung Cancer, Malignant Mesothelioma, Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), Paraffin Block.

Related studies

• A comparison of epidermal growth factor receptor expression in malignant peritoneal and pleural mesothelioma — Y. Enomoto, T. Kasai, et al. (2012)
• Patients with peritoneal mesothelioma lack epidermal growth factor receptor tyrosine kinase mutations that would make them sensitive to tyrosine kinase inhibitors — N. Kalra, A. Ashai, et al. (2012)
• Epidermal growth factor receptor mutations in 510 Finnish non--small-cell lung cancer patients — S. Mäki-Nevala, M. Rönty, et al. (2014)
• Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations — O. Rena, L.R. Boldorini, et al. (2011)
• Pulmonary adenocarcinoma with epidermal growth factor receptor-mutations in asbestos exposed non-smokers: A case series — R.L. Kradin, J. Iafrate, et al. (2017)
• 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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