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Updated: May 12, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samples of malignant pleural
R Mezzapelle1, U Miglio, O Rena
1Unit of Pathology, Department of Health Sciences, University of Eastern Piedmont Amedeo Avogadro, Via Solaroli 17, Novara 28100, Italy.
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.
Insights
Mutations in epidermal growth factor receptor (EGFR) downstream pathways are present in malignant pleural mesotheliomas (MPMs). While not directly linked to survival, these genetic alterations may help select patients for future clinical trials.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) plays a role in malignant pleural mesothelioma (MPM) pathogenesis.
- EGFR mutations or downstream pathway alterations can drive tumor growth, apoptosis resistance, and metastasis.
- Molecular profiling is crucial for identifying MPM patients who may benefit from anti-EGFR therapies.
Purpose of the Study:
- To investigate the frequency and prognostic significance of mutations in EGFR and its downstream pathways in MPM.
- To assess the potential of molecular profiling for patient selection in anti-EGFR therapy trials.
Main Methods:
- Genomic DNA was extracted from 77 MPM tissue samples.
- Real-time PCR and direct sequencing were used to detect EGFR mutations.
- Mutant-enriched PCR and direct sequencing were employed to identify KRAS, PIK3CA, and BRAF mutations.
Main Results:
- Mutations were found in 12% of MPM cases, including KRAS (5), BRAF (3), and PI3KCA (1).
- No EGFR gene mutations were detected in the study cohort.
- No significant difference in disease-specific survival was observed between patients with or without detected gene mutations.
Conclusions:
- Mutations within EGFR downstream pathways are relatively common in MPM.
- The identified mutations did not appear to have prognostic value in this study.
- These findings suggest that targeting downstream pathways may be relevant for future MPM patient selection in clinical trials.
