EGFR Status in Mesothelioma: Possible Implications for the Efficacy of Anti-EGFR and Anti-MET Therapies

Our plain-English summary of EGFR Status in Mesothelioma: Possible Implications for the Efficacy of Anti-EGFR and Anti-MET Therapies, by S. Salvi, S. Varesano, S. Boccardo, et al (Journal of Thoracic Oncology, 2016).

The study

• Authors: S. Salvi, S. Varesano, S. Boccardo, J.L. Ravetti, P.A. Canessa, M.P. Pistillo, P. Ferro, F. Fedeli, S. Roncella
• Journal: Journal of Thoracic Oncology
• Published: 2016;11(6):e78-80
• Type of article: Letter
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter, the authors reported epidermal growth factor receptor (EGFR) gene copy number in malignant mesothelioma (MM) and discussed what it might mean for targeted therapy with tyrosine kinase inhibitors (TKIs). They used fluorescence in situ hybridization (FISH) on the same paraffin-embedded MM tissue samples from 60 patients that they had studied in an earlier letter on MET gene status. The study was approved by the Liguria Region Ethics Committee in Italy, and all patients gave written informed consent. EGFR protein expression was assessed by immunohistochemistry. Using the University of Colorado Cancer Center scoring system, the authors found no EGFR amplification. Four of 60 MMs (6.7%), all epithelioid, showed high EGFR polysomy, with four to 10 EGFR signals in approximately 60% to 80% of tumor cells. All EGFR-positive MM cells also overexpressed membrane and cytoplasmic EGFR protein. Both EGFR and MET lie on chromosome 7. All four cases were the same cases the authors had previously reported as showing high MET polysomy. Citing other studies of resistance to single-agent TKIs, the authors suggested that simultaneous high EGFR and MET polysomy might reduce the efficacy of anti-EGFR or anti-MET monotherapy. They proposed that combined inhibition of EGFR and MET might be a better choice for MM with high chromosome 7 polysomy. They concluded that chromosome 7 copy number gain might be a predictive marker for combined targeted therapy, but that this needs evaluation in controlled trials.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This letter to the editor reported a laboratory study of tumor tissue from 60 patients with malignant mesothelioma. The authors used the same stored tissue samples they had earlier tested for the MET gene. They used fluorescence in situ hybridization, a method that counts gene copies in cells, to examine the EGFR gene, and tissue staining for the EGFR protein. They found no EGFR gene amplification in any sample. Four of the 60 mesotheliomas (6.7%), all of the epithelioid type, showed high EGFR polysomy, meaning extra copies of the gene. In all four, the tumor cells also showed overexpression of the EGFR protein. These were the same four cases the authors had previously reported as having high MET gene polysomy. Both genes lie on chromosome 7. The authors suggested that drugs blocking EGFR and MET together might be a better choice than either drug alone for such tumors. They suggested that chromosome 7 copy number gain might be one marker for choosing this combined treatment. They stated that whether chromosome 7 polysomy has a clinical application needs to be evaluated in controlled trials. The article did not discuss asbestos exposure.

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: Letter to the editor reporting a laboratory analysis of stored tumor tissue (gene copy testing by fluorescence in situ hybridization, plus protein staining)
• Who was studied: Paraffin-embedded tumor tissue samples from 60 patients with malignant mesothelioma. These were the same samples used in the authors' earlier MET study. The study was approved by the Liguria Region (Italy) Ethics Committee. Dates are not given.
• Exposure: The article studied no asbestos or other exposure. It examined EGFR gene copy number and EGFR protein in tumor tissue.
• Main results:
  • No EGFR gene amplification was found in any of the mesothelioma samples.
  • Four of 60 mesotheliomas (6.7%), all epithelioid, showed high EGFR polysomy. These tumors had 4 to 10 EGFR gene spots in approximately 60% to 80% of tumor cells.
  • All of the EGFR-positive mesothelioma cells also showed overexpression of EGFR protein in the cell membrane and cytoplasm.
  • The four cases with high EGFR polysomy were the same four cases the authors had previously reported as having high MET gene polysomy. Both genes are located on chromosome 7.
• The authors' conclusion: The authors suggested that inhibiting EGFR and MET at the same time with tyrosine kinase inhibitors might be a better choice than single-drug treatment for mesotheliomas with high chromosome 7 polysomy. They also suggested that chromosome 7 copy number gain might be one of the predictive markers for such combined therapy.
• Limitations the authors state:
  • The authors stated that whether chromosome 7 polysomy has a clinical application needs to be evaluated in controlled trials.

Topics

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

Medical terms in this study, explained in our Lexicon: EGFR, Mesothelioma, Malignant Mesothelioma, Targeted Therapy, Tyrosine Kinase Inhibitor, Fluorescence In Situ Hybridization (FISH), Informed Consent, Immunohistochemistry.

Related studies

• Perifosine as a potential novel anti-cancer agent inhibits EGFR/MET-AKT axis in malignant pleural mesothelioma — G. Pinton, A.G. Manente, et al. (2012)
• Amplification of MET in a Patient with Malignant Pleural Mesothelioma — S. Varesano, S. Salvi, et al. (2015)
• Targeted inhibition of multiple receptor tyrosine kinases in mesothelioma — W.B. Ou, C. Hubert, et al. (2011)
• Coactivation of receptor tyrosine kinases in malignant mesothelioma as a rationale for combination targeted therapy — M. Brevet, S. Shimizu, et al. (2011)
• Combined inhibition of MET and EGFR suppresses proliferation of malignant mesothelioma cells — K. Kawaguchi, H. Murakami, et al. (2009)
• Therapeutic antitumor efficacy of anti-epidermal growth factor receptor antibody, cetuximab, against malignant pleural mesothelioma — J. Kurai, H. Chikumi, et al. (2012)

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