Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma

Our plain-English summary of Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural mesothelioma, by R. Mezzapelle, U. Miglio, O. Rena, et al (British Journal of Cancer, 2013).

The study

• Authors: R. Mezzapelle, U. Miglio, O. Rena, A. Paganotti, S. Allegrini, J. Antona, F. Molinari, M. Frattini, G. Monga, O. Alabiso, R. Boldorini
• Journal: British Journal of Cancer
• Published: 2013;108(8):1743-9
• Cited by: 36 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: As epidermal growth factor receptor (EGFR) is involved in the pathogenesis of malignant pleural mesotheliomas (MPMs), the anti-EGFR drugs may be effective in treating MPM patients. Mutations of the EGFR gene or its downstream effectors may cause constitutive activation leading to cell proliferation, and the inhibition of apoptosis and metastases. Consequently, molecular profiling is essential for select patients with MPM who may respond to anti-EGFR therapies.

Methods: After manual macrodissection, genomic DNA was extracted from 77 histological samples of MPM: 59 epithelioid, 10 biphasic, and 8 sarcomatoid. Epidermal growth factor receptor gene mutations were sought by means of real-time polymerase chain reaction (PCR) and direct sequencing, KRAS gene mutations by mutant-enriched PCR, and PIK3CA and BRAF gene mutations by direct sequencing.

Results: Gene mutations were identified in nine cases (12%): five KRAS, three BRAF, and one PI3KCA mutation; no EGFR gene mutations were detected. There was no difference in disease-specific survival between the patients with or without gene mutations (P=0.552).

Conclusions: Mutations in EGFR downstream pathways are not rare in MPM. Although none of those found in this study seemed to be prognostically significant, they may support a more specific selection of patients for future trials.

In plain English

This laboratory study looked for gene mutations in tumour samples from 77 consecutive patients with malignant pleural mesothelioma diagnosed at the University Hospital of Novara, Italy, between January 2008 and December 2010 (59 epithelioid, 10 biphasic, 8 sarcomatoid). Fifty patients (64.9%) had been exposed to asbestos at work. The article does not name fiber types. The authors tested the EGFR gene and three genes in its signalling pathway: KRAS, BRAF and PIK3CA. No EGFR mutations were found. Nine patients (12%) had mutations: five in KRAS, three in BRAF and one in PIK3CA. All five patients with KRAS mutations reported occupational asbestos exposure, and none of the four with BRAF or PIK3CA mutations did. Disease-specific survival did not differ between patients with and without mutations. Among asbestos-exposed patients, those with KRAS mutations had shorter mean survival (9.20 vs 15.6 months), but this difference was not statistically significant. The authors concluded that such mutations are not rare in this cancer and may help select patients for future trials. They said their findings need confirming in larger series.

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 gene-mutation analysis of tumour biopsy samples from a consecutive series of patients, with comparison of clinical features and disease-specific survival between patients with and without mutations
• Who was studied: 77 consecutive patients with malignant pleural mesothelioma admitted to the Thoracic Unit of the University Hospital of Novara (Italy) between January 2008 and December 2010. There were 57 males and 20 females. Tumours were 59 epithelioid, 10 biphasic and 8 sarcomatoid.
• Exposure: Previous occupational asbestos exposure was reported by 50 of the 77 patients (64.9%). Fiber types, products, jobs and doses are not reported. The main focus of the study was mutations in the EGFR, KRAS, BRAF and PIK3CA genes.
• Main results:
  • Mutations in the EGFR downstream pathway were found in 9 of 77 patients (12%): five in KRAS, three in BRAF and one in PIK3CA.
  • No mutations were found in the EGFR gene itself in any of the 77 samples.
  • Disease-specific survival did not differ between patients with and without gene mutations (P = 0.552).
  • All patients with KRAS mutations reported occupational asbestos exposure. None of the patients with BRAF or PIK3CA mutations did.
  • Among patients with reported asbestos exposure, the 5 with KRAS mutations had a mean survival of 9.20 months, compared with 15.6 months for those with wild-type (unmutated) KRAS (n = 42). The difference was not statistically significant (P = 0.188).
  • Among patients without reported occupational asbestos exposure, the 3 with BRAF mutations had a mean survival of 20.33 months, compared with 12.1 months for those without BRAF mutations (n = 22). The difference was not statistically significant (P = 0.140).
  • The presence or absence of mutations showed no significant differences by gender, age, occupational asbestos exposure, previous cancer, histological type, performance status or treatment.
• The authors' conclusion: The authors concluded that mutations in EGFR downstream pathways are not rare in malignant pleural mesothelioma. None of those found appeared prognostically significant, but they may support more specific selection of patients for future trials.
• Limitations the authors state:
  • The survival differences by KRAS and BRAF mutation status were not statistically significant, and the findings need confirmation in larger series of patients.
  • The clinical implications of the mutations found are not clear.

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, Apoptosis, Molecular Profiling, Epithelioid, Biphasic Mesothelioma, Sarcomatoid.

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