Zakaria Zubaidah, Zulkifle Muhamad Farid, Wan Hasan Wan Atiqah Najiah, Azhari Azlah Kamilah, Abdul Raub Sayyidi Hamzi, Eswaran Jeyanthy, Soundararajan Meera, Syed Husain Sharifah Noor Akmal
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.
Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Cheras, Kuala Lumpur 56000, Malaysia.
Onco Targets Ther. 2019 Sep 20;12:7749-7756. doi: 10.2147/OTT.S214611. eCollection 2019.
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.
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.
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.
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.
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.
表皮生长因子受体(EGFR)是酪氨酸激酶受体蛋白ErbB家族的成员,在肿瘤细胞存活和增殖中起重要作用。据报道,高达78%的三阴性乳腺癌(TNBC)病例中EGFR过表达,这表明它是一个潜在的治疗靶点。抗EGFR药物在乳腺癌中的临床试验显示缓解率较低。然而,有一部分患者对EGFR抑制剂有反应,这突出了对患者进行分层的必要性,这些患者可能受益于包括抗EGFR药物在内的有效联合治疗。EGFR表达的人群变异性需要在特定人群中进行系统评估。
研究马来西亚多民族TNBC患者队列中EGFR的改变和表达,以确定对该人群使用抗EGFR联合治疗的可能性。
在本研究中,我们分别使用荧光原位杂交(FISH)和免疫组织化学(IHC)方法评估了58例马来西亚TNBC患者样本的EGFR基因拷贝数改变和EGFR蛋白过表达情况。
约30%的患者观察到EGFR蛋白过表达,而15.5%的患者显示EGFR拷贝数高,包括5.17%的基因扩增和超过10%的高多倍体。EGFR蛋白过表达与基因拷贝数之间存在正相关,在48例无基因扩增的低拷贝数病例中有10例(20.9%)观察到EGFR过表达。
本研究首次展示了马来西亚多民族TNBC患者队列中EGFR的改变和表达,强调了在马来西亚进行全国范围内大规模EGFR表达评估的必要性。