Rabab Gaafar¹, Abeer Bahnassy², Ahmed Bastawissy¹, Hala Aziz¹, Anan O Abdel-Aleem³, Emad R Issak⁴* and Nagla Karim⁵

¹Medical Oncology department, National Cancer Institute, Cairo University, Cairo, Egypt
²Tissue culture and Cytogenetics Unit, Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt
³Cancer Biology Department, NCI, Cairo University, Cairo, Egypt
⁴Immunology Department, Ain Shams University, Cairo, Egypt
⁵Medical Oncology Department, Georgia institute, USA

*Corresponding Author: Emad R Issak, Immunology Department, Ain Shams University, Cairo, Egypt.

Received: May 01, 2022; Published: June 03, 2022

Abstract

Objectives: The study was to assess frequency and patterns of Epidermal Growth Factor Receptor (EGFR) mutation status in a cohort of Egyptian patients with Non-Small Cell Lung Cancer (NSCLC) from the National Cancer Institute (NCI), Cairo University. Also, it aimed to investigate the association of the EGFR mutation status to several clinico-pathological features of patients.

Methods: EGFR mutation status was assessed in tumor tissue samples of 141 NSCLC patients from Egypt presenting to the NCI, Cairo University from December 2014 to January 2018. The association of EGFR mutation status to the relevant clinical and pathological features of the patients was studied using the logistic regression.

Results: EGFR mutations were detected in 33 (23.4%) patients. The most detected were 19 Del (18 patients; 12.77%), exon 21 (13 patients; 9.22%), exon 21+T790M, and G719X (one patient; 0.71%); each. EGFR mutation status was associated significantly to advanced disease stage (p < 0.001), brain metastasis 8/19 (42.11%, p = 0.049) and contralateral lung metastasis 7/14 (50%, p = 0.038). EGFR mutations were also higher in females (non-smokers (35%) and in males smokers (20.9%, p < 0.001). Multivariate analysis showed that only the contralateral lung metastasis is an independent predictor for EGFR mutations in the NSCLC patients.

Conclusion: EGFR mutations are relatively common (23.4%) in NSCLC patients from Egypt (NCI experience). Therefore, testing for EGFR mutations in NSCLC should be done routinely for those patients for better treatment outcomes.

Keywords: NSCLC; EGFR Mutations; Exons 19, 21, T790M and Metastasis

References

1. Bade BC and Dela Cruz CS. "Lung Cancer 2020: Epidemiology, Etiology, and Prevention”. Clinics in Chest Medicine 1 (2020): 1-24.
2. Bray F., et al. “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries”. CA: A Cancer Journal for Clinicians (2018): 3-31.
3. Ibrahim AS., et al. “Cancer Incidence in Egypt: Results of the National Population-Based Cancer Registry Program”. Journal of Cancer Epidemiology (2014): e437971.
4. Wang S and Wang Z. “EGFR mutations in patients with non-small cell lung cancer from mainland China and their relationships with clinicopathological features: a meta-analysis”. International Journal of Clinical and Experimental Medicine 8 (2014): 1967-1978.
5. Liu L and Wei S. “Research Progress of KRAS Mutation in Non-small Cell Lung Cancer” 21.5 (2018): 419-424.
6. Doebele RC and Camidge DR. “Targeting ALK, ROS1, and BRAF kinases”. Journal of Thoracic Oncology 7 (2012): S375-376.
7. Lynch TJ., et al. “Activating mutations in the epidermal growth factor receptor underlying responsiveness of non small cell lung cancer to gefitinib”. The New England Journal of Medicine 350 (2004): 2129-2139.
8. Takeda M., et al. “First- and Second-Generation EGFR-TKIs Are All Replaced to Osimertinib in Chemo-Naive EGFR Mutation-Positive Non-Small Cell Lung Cancer?”. International Journal of Molecular Sciences 1 (2019): 146.
9. Cross DA., et al. “AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer”. Cancer Discovery 4 (2014): 1046-1061.
10. Maemondo M., et al. “Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR”. The New England Journal of Medicine 362 (2010): 2380-2388.
11. Mitsudomi T., et al. “Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial”. Lancet Oncology11 (2010): 121-128.
12. Zhou C., et al. “Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study”. Lancet Oncology 12 (2011): 735-742.
13. Rosell R., et al. “Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial”. Lancet Oncology 13 (2012): 239-246.
14. Sequist LV., et al. “Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations”. Journal of Clinical Oncology 31 (2013): 3327-3334.
15. Wu YL., et al. “Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): An open-label, randomised phase 3 trial”. Lancet Oncology 15 (2014): 213-222.
16. Cross DA., et al. “An irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFRinhibitors in lung cancer”. Cancer Discover 4 (2014): 1046-1061.
17. Lai Y., et al. “EGFR Mutations in Surgically Resected Fresh Specimens from 697 Consecutive Chinese Patients with Non-Small Cell Lung Cancer and Their Relationships with Clinical Features”. International Journal of Molecular Sciences 14 (2013): 24549-24559. 
18. Eid SSM., et al. “Mutation of EGFR in Non-small Cell Lung Cancer, a Regional Study in Upper Egypt”. Cancer Research Journal1 (2020): 1.
19. Roengvoraphoj M., et al. “Epidermal growth factor receptor tyrosine kinase inhibitors as initial therapy for non-small cell lung cancer: focus on epidermal growth factor receptor mutation testing and mutation-positive patients”. Cancer Treatment Review8 (2013): 839-850.
20. Yamaoka T., et al. “Molecular-targeted therapies for epidermal growth factor receptor and its resistance mechanisms”. International Journal of Molecular Sciences 11 (2017): E2420.
21. Cappuzzo F., et al. “EGFR and HER2 gene copy number and response to first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC)”. Journal of Thoracic Oncology5 (2007): 423-429.
22. Demiray A., et al. “The frequency of EGFR And KRAS mutations in the Turkish population with non-small cell lung cancer and their response to erlotinib therapy”. Balkan Journal of Medical Genetics: BJMG2 (2018): 21.
23. Jazieh AR., et al. “Patterns of epidermal growth factor receptor mutation in non-small-cell lung cancers in the Gulf region”. Molecular and Clinical Oncology6 (2015): 1371-1374.
24. Graham RP., et al. “Worldwide Frequency of Commonly Detected EGFR Mutations”. Archives of Pathology and Laboratory Medicine 2 (2018): 163-167.
25. Shi Y., et al. “A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER)”. Journal of Thoracic Oncology2 (2014): 154-162.
26. Sahoo R., et al. “Screening for EGFR mutations in lung cancer, a report from India”. Lung Cancer3 (2011): 316-319.
27. Chougule A., et al. “Frequency of EGFR mutations in 907 lung adenocarcioma patients of Indian ethnicity”. PLoS One10 (2011): e76164.
28. Sekine I., et al. “Emerging ethnic differences in lung cancer therapy”. British Journal of Cancer11 (2008): 1757-1762.
29. Zaki MA., et al. “Nonenriched PCR Versus Mutant-Enriched PCR in Detecting Selected Epidermal Growth Factor Receptor Gene Mutations Among Non small-Cell Lung Cancer Patients”. Genetic Testing and Molecular Biomarkers 8 (2015): 444-449.
30. Helmy N., et al. “The frequency of epidermal growth factor receptor mutations in non-small-cell lung cancer patients from Egypt”. Egyptian Journal of Pathology 35 (2015): 24-29.
31. Gaur P., et al. “EGFR Mutation Detection and Its Association With Clinicopathological Characters of Lung Cancer Patients”. World Journal of Oncology5-6 (2018): 151.
32. Demiray A., et al. “The frequency of EGFR And KRAS mutations in the Turkish population with non-small cell lung cancer and their response to erlotinib therapy”. Balkan Journal of Medical Genetics: BJMG2 (2018): 21.
33. Jazieh AR., et al. “Patterns of epidermal growth factor receptor mutation in non-small-cell lung cancers in the Gulf region”. Molecular and Clinical Oncology 6 (2015): 1371-1374.

Citation

Citation: Rabab Gaafar., et al. “Epidermal Growth Factor Receptor (EGFR) Mutation Status in Egyptian Patients with Non-Small Cell Lung Cancer (NSCLC); Can it be Predicted?: Acta Scientific Cancer Biology 6.7 (2022): .

Copyright

Copyright: © 2022 Emad R Issak., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.