Epidermal growth factor receptor mutations in 510 Finnish non--small-cell lung cancer patients

Our plain-English summary of Epidermal growth factor receptor mutations in 510 Finnish non--small-cell lung cancer patients, by S. Mäki-Nevala, M. Rönty, M. Morel, et al (Journal of Thoracic Oncology, 2014).

The study

• Authors: S. Mäki-Nevala, M. Rönty, M. Morel, M. Gomez, Z. Dawson, V.K. Sarhadi, A. Telaranta-Keerie, A. Knuuttila, S. Knuutila
• Journal: Journal of Thoracic Oncology
• Published: 2014;9(6):886-91
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Among the driver gene mutations in non-small-cell lung cancer, mutations in epidermal growth factor receptor (EGFR) are the most important because of their predictive role in selecting patients eligible for targeted therapy. Our aim was to study EGFR mutations in a Finnish non-small-cell lung cancer cohort of 528 patients.

Methods: Mutation testing was conducted on DNA extracted from paraffin-embedded, formalin-fixed tumor material using the following real-time polymerase chain reaction-based kits: Therascreen EGFR PCR Kit and cobas EGFR Mutation Test.

Results: EGFR mutation frequency was 11.4% and all positive cases were adenocarcinomas, of which a majority had an acinar predominant pattern. Mutations were seen significantly more often in females and never-smokers than in males and smokers. The most frequent mutations were L858R in exon 21 and deletions in exon 19. Overall survival of the patients, not treated with EGFR inhibitor, did not differ between EGFR mutation-positive and EGFR mutation-negative patients.

Conclusion: EGFR mutation profile in this Finnish non-small-cell lung cancer cohort resembles in many respect with that of other Western European cohorts, even though the overall frequency of mutations is slightly higher. We show the occurrence of EGFR mutations in patients with occupational asbestos exposure and also in those diagnosed with chronic obstructive pulmonary disease who have not been often investigated before.

In plain English

This brief report examined EGFR gene mutations in tumor samples from Finnish non-small-cell lung cancer patients treated in the Hospital District of Helsinki and Uusimaa from 2006 to 2012. Of 528 patients tested with commercial PCR kits, 510 gave a result. EGFR mutations were found in 11.4% (58 of 510), all in adenocarcinomas. Mutations were more common in women (16.6%) than in men (6.7%), and in never-smokers (32.8%) than in ever-smokers (8.2%). Occupational asbestos exposure was established from patient interviews. Among exposed patients, 10.9% (5 of 46) had mutations, compared with 9.6% (21 of 219) of non-exposed patients. The reported p-value for asbestos was 0.498, which is not statistically significant; that test also included 245 patients with uncertain exposure information. The five exposed patients with mutations had no diagnosis of asbestosis or pleural plaques. Among adenocarcinoma patients not given EGFR-inhibitor drugs, survival did not differ significantly by mutation status. The authors concluded that the Finnish mutation profile resembled that of other European cohorts. They suggested the slightly higher frequency may reflect the many adenocarcinomas and the test used. They said larger studies are needed on asbestos exposure and EGFR mutations.

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 (brief report) of EGFR mutation testing in tumor samples
• Who was studied: Finnish Caucasian non-small-cell lung cancer patients treated in the Hospital District of Helsinki and Uusimaa (HUS), Finland, 2006 to 2012. Specimens were collected for 613 patients, 528 were tested and 510 gave a result.
• Exposure: EGFR mutation status was compared across patient characteristics including sex, smoking, COPD and occupational asbestos exposure. Asbestos exposure was established from patient interviews. No fiber types or doses were reported.
• Main results:
  • EGFR mutations were found in 11.4% of all patients with a test result (58 of 510).
  • All mutations occurred in adenocarcinomas.
  • Mutations were more frequent in women (16.6%, 40 of 241) than in men (6.7%, 18 of 269), p less than 0.001.
  • Mutations were more frequent in never-smokers (32.8%, 22 of 67) than in ever-smokers (8.2%, 36 of 438), p less than 0.001.
  • Among patients with occupational asbestos exposure, 10.9% (5 of 46) had EGFR mutations. The reported p-value was 0.498. In Table 1 this p-value applies to the asbestos variable as a whole, which also includes 245 patients with no sure exposure information (13.1%, 32 of 245, with mutations).
  • Among non-exposed patients, 9.6% (21 of 219) had EGFR mutations.
  • The five asbestos-exposed patients with EGFR mutations had not been diagnosed with asbestos-related diseases (asbestosis or pleural plaques). All five were men and all had a history of smoking.
  • Mutations were less frequent in patients with COPD (6.3%, 7 of 111) than in those without COPD (12.8%, 51 of 399). The difference was not statistically significant (p = 0.057).
  • The most frequent mutations were L858R in exon 21, at 41.4% (24 of 58), and deletions in exon 19, at 36.2% (21 of 58) of all mutations.
  • Adenocarcinoma patients not treated with EGFR inhibitors were compared by mutation status. Mean overall survival was 68.6 months (95% confidence interval 62.6 to 74.7) for patients without the mutation and 52.2 months (95% confidence interval 40.2 to 64.2) for patients with it. The difference was not statistically significant (p = 0.460).
• The authors' conclusion: The authors concluded that the EGFR mutation profile in this Finnish cohort resembled in many respects that of other Western European cohorts, although the overall mutation frequency was slightly higher. They attributed this most likely to the high proportion of adenocarcinoma in the cohort.
• Limitations the authors state:
  • The authors noted that the type of mutation test used may have affected the results.
  • The authors stated that larger studies are needed to study the influence of asbestos exposure on EGFR mutations.

Topics

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

Medical terms in this study, explained in our Lexicon: Lung Cancer, EGFR, Targeted Therapy, Adenocarcinoma, Acinar, Overall Survival, Asbestos Exposure.

Related studies

• Pulmonary adenocarcinoma with epidermal growth factor receptor-mutations in asbestos exposed non-smokers: A case series — R.L. Kradin, J. Iafrate, et al. (2017)
• Hot spot mutations in Finnish non-small cell lung cancers — S. Mäki-Nevala, V.K. Sarhadi, et al. (2016)
• 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 malignant pleural and peritoneal mesothelioma — Y. Enomoto, T. Kasai, et al. (2012)
• Epidermal growth factor receptor overexpression in malignant pleural mesothelioma: prognostic correlations — O. Rena, L.R. Boldorini, et al. (2011)
• Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers — J.C. Pache, Y.M. Janssen, et al. (1998)

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