Very low prevalence of epidermal growth factor receptor (EGFR) protein expression and gene amplification in Saudi breast cancer patients
© Shawarby et al; licensee BioMed Central Ltd. 2011
Received: 8 April 2011
Accepted: 24 June 2011
Published: 24 June 2011
Breast cancers which demonstrate EGFR protein expression, gene amplification and/or gene mutations may benefit therapeutically from tyrosine kinase inhibitors. In Western studies, EGFR protein expression has been demonstrated in 7-36% of breast cancer patients, while gene amplification has been found in around 6% of cases and mutations were either absent or extremely rare. Studies addressing EGFR protein expression and gene amplification in Saudi breast cancer patients are extremely scanty and the results reported have been mostly non-conclusive. Herein we report the prevalence of EGFR protein expression and gene amplification in a cohort of Saudi breast cancer patients.
We noticed a remarkably low incidence of EGFR protein expression (1.3%) while analyzing the spectrum of molecular subtypes of breast cancer in a Saudi population by immunohistochemistry. Also, EGFR gene amplification could not be demonstrated in any of 231 cases studied using silver enhanced in situ hybridization.
The extremely low incidence of EGFR protein expression and gene amplification in Saudi breast cancer patients as compared to Western populations is most probably ethnically related as supported by our previous finding in the same cohort of a spectrum of molecular breast cancer types that is unique to the Saudi population and in stark contrast with Western and other regionally based studies. Further support to this view is provided by earlier studies from Saudi Arabia that have similarly shown variability in molecular breast cancer subtype distribution between Saudi and Caucasian populations as well as a predominance of the high-grade pathway in breast cancer development in Middle East women. More studies on EGFR in breast cancer are needed from different regions of Saudi Arabia before our assumption can be confirmed, however.
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Background and research hypothesis
EGFR is a tyrosine kinase receptor in the HER family which is widely expressed in a number of epithelial tumors and is believed to play a key role in cell proliferation. It is now well established that non-small-cell lung cancers which demonstrate EGFR protein expression, gene amplification and/or gene mutations at exons 18 - 21 show a dramatic therapeutic response to tyrosine kinase inhibitors such as gefitinib and erlotinib [1–3]. Although the same may be true for other cancers including breast cancer, data regarding the presence or absence of EGFR abnormalities in tumors other than lung cancer and the response of such tumors to anti EGFR therapy are still limited and rather conflicting. EGFR protein expression as assessed by immunohistochemistry has been demonstrated in 7-36% of breast cancer patients, while gene amplification as assessed by CISH or FISH has been found in around 6% of cases [4–8]. Mutations in exons 18 - 21 of the EGFR gene investigated by PCR were either absent [1, 7] or present in only rare breast cancer patients , such mutations being much frequent in lung cancer . Differences in the prevalence of EGFR over-expression reported by different studies have been attributed to probable variations in techniques and type of antibodies used, criteria for determining over-expression and inter-observer variability .
In a recent study that analyzed the spectrum of molecular subtypes of breast cancer in a Saudi population , we noticed (but have not reported) a remarkably low incidence of EGFR protein expression in our patients. Also, EGFR gene amplification could not be demonstrated in any of 231 cases studied using silver enhanced in situ hybridization (assessed after the study was published). In this article we aim to explore whether this extremely low incidence of protein expression and gene amplification reflects a truly low prevalence of EGFR gene abnormalities in the Saudi population which may be ethnically related or is, alternatively, due to possible suboptimal sensitivity of the immunohistochemistry technique/antibodies or the in situ hybridization method used.
Patients, methods and results
Histolopathogical and molecular characteristics of cancer in a cohort of 231 Saudi breast cancer patients
Immunohistochemical findings and Ki67 index in EGFR positive breast cancer cases
Histologic type in relation to patient age, tumor grade and tumor stage in EGFR positive breast cancer cases
Patient age (years)
Invasive ductal carcinoma, NOS
Comment, conclusions and recommendation
Prevalence of EGFR protein expression and gene amplification in present study compared to Western studies
A better approach to verify our assumption, however, would be to attempt confirming an extremely low prevalence of EGFR gene amplification in Saudi patients using PCR which is a more sensitive method than all in situ hybridization techniques. Moreover, by PCR, we can explore mutations at various exons of the EGFR gene, which may not necessarily be reflected as gene amplification or protein expression but are still effective in determining prognosis and response to anti EGFR therapy. Studies addressing EGFR protein expression and gene amplification in Saudi breast cancer patients are extremely scanty and the results reported have been mostly non-conclusive . More studies in this direction are encouraged from different regions of Saudi Arabia.
List of abbreviations
Chromagenic in situ hybridization
Epidermal growth factor receptor
Fluorescent in situ hybridization
Human epidermal growth factor receptor
In situ hybridization
Polymerase chain reaction
Silver enhanced in situ hybridization
We acknowledge the services of Mrs Khalda Al Johy, Mr Shakir Ahmad and Mrs Maria Rosario Lazaro for conducting the laboratory work.
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