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Epidermal growth factor receptor (EGFR) gene alteration and protein overexpression in Malaysian triple-negative breast cancer (TNBC) cohort

Authors Zakaria Z, Zulkifle MF, Wan Hasan WAN, Azhari AK, Abdul Raub SH, Eswaran J, Soundararajan M, Syed Husain SNA

Received 16 May 2019

Accepted for publication 18 July 2019

Published 20 September 2019 Volume 2019:12 Pages 7749—7756

DOI https://doi.org/10.2147/OTT.S214611

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Rachel Predeepa

Peer reviewer comments 2

Editor who approved publication: Dr Gaetano Romano


Zubaidah Zakaria,1 Muhamad Farid Zulkifle,1–3 Wan Atiqah Najiah Wan Hasan,1 Azlah Kamilah Azhari,2,4 Sayyidi Hamzi Abdul Raub,2,4 Jeyanthy Eswaran,5,6 Meera Soundararajan,7 Sharifah Noor Akmal Syed Husain2,4

1Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health (MOH), Setia Alam, Shah Alam 40170, Selangor Darul Ehsan, Malaysia; 2Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Cheras, Kuala Lumpur 56000, Malaysia; 3Nutrition, Metabolism and Cardiovascular Research Centre (NMCRC), Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health (MOH), Setia Alam, 40170 Shah Alam, Selangor Darul Ehsan, Malaysia; 4Reference Specialised Laboratory, Pantai Premier Pathology Sdn. Bhd., Kuala Lumpur 59100, Malaysia; 5Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, NE1 7RU, UK; 6Newcastle University Medicine Malaysia, Gelang Patah, Johor 79200, Malaysia; 7Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle-upon-Tyne NE1 8ST, UK

Correspondence: Zubaidah Zakaria
Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institutes of Health (NIH), Ministry of Health (MOH), Setia Alam, Shah Alam 40170, Selangor Darul Ehsan, Malaysia
Tel +60 33 362 7622
Fax +60 33 362 7905
Email zubaidah@imr.gov.my

Sayyidi Hamzi Abdul Raub
Reference Specialised Laboratory, Pantai Premier Pathology Sdn. Bhd., Kuala Lumpur 59100, Malaysia
Tel +60 32 282 8795
Fax +60 32 282 0187
Email sayyidi.hamzi@parkwaypantai.com

Background: Epidermal growth factor receptor (EGFR) is a member of the ErbB family of tyrosine kinase receptor proteins that plays important roles in tumour cell survival and proliferation. EGFR has been reported to be overexpressed in up to 78% of triple-negative breast cancer (TNBC) cases suggesting it as a potential therapeutic target. The clinical trials of anti-EGFR agents in breast cancer showed low response rates. However, a subgroup of patients demonstrated response to EGFR inhibitors highlighting the necessity to stratify patients, who might benefit from effective combination therapy that could include anti EGFR-agents. Population variability in EGFR expression warrants systematic evaluation in specific populations.
Purpose: To study EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort to determine the possibility of using anti-EGFR combinatorial therapy for this population.
Patients and methods: In this study, we evaluated 58 cases of Malaysian TNBC patient samples for EGFR gene copy number alteration and EGFR protein overexpression using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) methods, respectively.
Results: EGFR protein overexpression was observed in about 30% while 15.5% displayed high EGFR copy number including 5.17% gene amplification and over 10% high polysomy. There is a positive correlation between EGFR protein overexpression and gene copy number and over expression of EGFR is observed in ten out of the 48 low copy number cases (20.9%) without gene amplification.
Conclusion: This study provides the first glimpse of EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort emphasising the need for the nationwide large scale EGFR expression evaluation in Malaysia.

Keywords: FISH, fluorescence in situ hybridization, IHC, immunohistochemistry, TNBC biomarker, metastatic breast cancer

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