Skip to main content
Top
Published in: Diagnostic Pathology 1/2011

Open Access 01-12-2011 | Short report

Very low prevalence of epidermal growth factor receptor (EGFR) protein expression and gene amplification in Saudi breast cancer patients

Authors: Mohamed A Shawarby, Dalal M Al-Tamimi, Ayesha Ahmed

Published in: Diagnostic Pathology | Issue 1/2011

Login to get access

Abstract

Background

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.

Findings

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.

Conclusions

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.

Virtual Slides

The virtual slide(s) for this article can be found here: http://​www.​diagnosticpathol​ogy.​diagnomx.​eu/​vs/​1171467253537062​.
Appendix
Available only for authorised users
Literature
1.
go back to reference Lynch TJ, Bell DW, Sordella R, et al.: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004, 350: 2129-2139. 10.1056/NEJMoa040938.CrossRefPubMed Lynch TJ, Bell DW, Sordella R, et al.: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004, 350: 2129-2139. 10.1056/NEJMoa040938.CrossRefPubMed
2.
go back to reference Paez JG, Janne PA, Lee JC, et al.: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004, 304: 1497-1500. 10.1126/science.1099314.CrossRefPubMed Paez JG, Janne PA, Lee JC, et al.: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004, 304: 1497-1500. 10.1126/science.1099314.CrossRefPubMed
3.
go back to reference Pao W, Miller V, Zakowski M, et al.: EGF receptor gene mutations are common in lung cancers from 'never smokers' and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA. 2004, 101: 13306-13311. 10.1073/pnas.0405220101.PubMedCentralCrossRefPubMed Pao W, Miller V, Zakowski M, et al.: EGF receptor gene mutations are common in lung cancers from 'never smokers' and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci USA. 2004, 101: 13306-13311. 10.1073/pnas.0405220101.PubMedCentralCrossRefPubMed
4.
go back to reference Harris AL, Nicholson S, Sainsbury JR, et al.: Epidermal growth factor receptors in breast cancer: association with early relapse and death, poor response to hormones and interactions with neu. J Steroid Biochem. 1989, 34: 123-131. 10.1016/0022-4731(89)90072-1.CrossRefPubMed Harris AL, Nicholson S, Sainsbury JR, et al.: Epidermal growth factor receptors in breast cancer: association with early relapse and death, poor response to hormones and interactions with neu. J Steroid Biochem. 1989, 34: 123-131. 10.1016/0022-4731(89)90072-1.CrossRefPubMed
5.
go back to reference Tsutsui S, Kataoka A, Ohno S, et al.: Prognostic and predictive value of epidermal growth factor receptor in recurrent breast cancer. Clin Cancer Res. 2002, 8: 3454-3460.PubMed Tsutsui S, Kataoka A, Ohno S, et al.: Prognostic and predictive value of epidermal growth factor receptor in recurrent breast cancer. Clin Cancer Res. 2002, 8: 3454-3460.PubMed
6.
go back to reference Walker RA, Dearing SJ: Expression of epidermal growth factor receptor mRNA and protein in primary breast carcinomas. Breast Cancer Res Treat. 1999, 53: 167-176. 10.1023/A:1006194700667.CrossRefPubMed Walker RA, Dearing SJ: Expression of epidermal growth factor receptor mRNA and protein in primary breast carcinomas. Breast Cancer Res Treat. 1999, 53: 167-176. 10.1023/A:1006194700667.CrossRefPubMed
7.
go back to reference Bhargava R, Gerald WL, Li AR, et al.: EGFR gene amplification in breast cancer: correlation with epidermal growth factor mRNA and protein expression and Her-2 status and absence of EGFR-activating mutations. Modern Pathology. 2005, 18: 1027-1033. 10.1038/modpathol.3800438.CrossRefPubMed Bhargava R, Gerald WL, Li AR, et al.: EGFR gene amplification in breast cancer: correlation with epidermal growth factor mRNA and protein expression and Her-2 status and absence of EGFR-activating mutations. Modern Pathology. 2005, 18: 1027-1033. 10.1038/modpathol.3800438.CrossRefPubMed
8.
go back to reference Press MF, Finn RS, Di Leo A, et al.: Correlation of HER2 gene amplification, HER2 and EGFR expression (protein and mRNA) with lapatinib efficacy in women with metastatic breast cancer. J Clin Oncol. 2008, 26: (May 20 suppl; abstr 1007) Press MF, Finn RS, Di Leo A, et al.: Correlation of HER2 gene amplification, HER2 and EGFR expression (protein and mRNA) with lapatinib efficacy in women with metastatic breast cancer. J Clin Oncol. 2008, 26: (May 20 suppl; abstr 1007)
9.
go back to reference Generali D, Leek R, Fox SB, et al.: EGFR mutations in exons 18-21 in sporadic breast cancer. Ann Oncol. 2007, 18: 203-205.CrossRefPubMed Generali D, Leek R, Fox SB, et al.: EGFR mutations in exons 18-21 in sporadic breast cancer. Ann Oncol. 2007, 18: 203-205.CrossRefPubMed
10.
go back to reference Liang Z, Zhang J, Zeng X, et al.: Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas. BMC cancer. 2010, 10: 376-10.1186/1471-2407-10-376.PubMedCentralCrossRefPubMed Liang Z, Zhang J, Zeng X, et al.: Relationship between EGFR expression, copy number and mutation in lung adenocarcinomas. BMC cancer. 2010, 10: 376-10.1186/1471-2407-10-376.PubMedCentralCrossRefPubMed
11.
go back to reference Al Tamimi DM, Shawarby MA, Ahmed A, et al.: Protein expression profile and prevalence pattern of the molecular classes of breast cancer - a Saudi population based study. BMC Cancer. 2010, 10: 223-10.1186/1471-2407-10-223.PubMedCentralCrossRefPubMed Al Tamimi DM, Shawarby MA, Ahmed A, et al.: Protein expression profile and prevalence pattern of the molecular classes of breast cancer - a Saudi population based study. BMC Cancer. 2010, 10: 223-10.1186/1471-2407-10-223.PubMedCentralCrossRefPubMed
12.
go back to reference Reis-Filho JS, Milanezi F, Carvalho S, et al.: Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromagenic in situ hybridization analysis. Breast Cancer Research. 2005, 7: R1028-R1035. 10.1186/bcr1341.PubMedCentralCrossRefPubMed Reis-Filho JS, Milanezi F, Carvalho S, et al.: Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromagenic in situ hybridization analysis. Breast Cancer Research. 2005, 7: R1028-R1035. 10.1186/bcr1341.PubMedCentralCrossRefPubMed
13.
go back to reference Kim MJ, Ro JY, Ahn SH, et al.: Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and HER2/neu-overexpressing phenotypes. Hum Pathol. 2006, 37: 1217-1226. 10.1016/j.humpath.2006.04.015.CrossRefPubMed Kim MJ, Ro JY, Ahn SH, et al.: Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and HER2/neu-overexpressing phenotypes. Hum Pathol. 2006, 37: 1217-1226. 10.1016/j.humpath.2006.04.015.CrossRefPubMed
14.
go back to reference Carey LA, Perou CM, Livasy CA, et al.: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006, 295: 2492-2502. 10.1001/jama.295.21.2492.CrossRefPubMed Carey LA, Perou CM, Livasy CA, et al.: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006, 295: 2492-2502. 10.1001/jama.295.21.2492.CrossRefPubMed
15.
go back to reference Cheang MCU, Chia SK, Voduc D, et al.: Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer. J Natl Cancer Inst. 2009, 101: 736-750. 10.1093/jnci/djp082.PubMedCentralCrossRefPubMed Cheang MCU, Chia SK, Voduc D, et al.: Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer. J Natl Cancer Inst. 2009, 101: 736-750. 10.1093/jnci/djp082.PubMedCentralCrossRefPubMed
16.
go back to reference Bhargava R, Striebel J, Beriwal S, et al.: Prevalence, Morphologic Features and Proliferation Indices of Breast Carcinoma Molecular Classes Using Immunohistochemical Surrogate Markers. Int J clin Exp Pathol. 2009, 2: 444-455.PubMedCentralPubMed Bhargava R, Striebel J, Beriwal S, et al.: Prevalence, Morphologic Features and Proliferation Indices of Breast Carcinoma Molecular Classes Using Immunohistochemical Surrogate Markers. Int J clin Exp Pathol. 2009, 2: 444-455.PubMedCentralPubMed
17.
go back to reference Tamimi RM, Baer HJ, Marotti J, et al.: Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Research. 2008, 10: R67-10.1186/bcr2128.PubMedCentralCrossRefPubMed Tamimi RM, Baer HJ, Marotti J, et al.: Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Research. 2008, 10: R67-10.1186/bcr2128.PubMedCentralCrossRefPubMed
18.
go back to reference Adebamowo CA, Famooto A, Ogundiran TO, et al.: Immunohistochemical and molecular subtypes of breast cancer in Nigeria. Breast cancer research and treatment. 2007, 110: 183-188.CrossRefPubMed Adebamowo CA, Famooto A, Ogundiran TO, et al.: Immunohistochemical and molecular subtypes of breast cancer in Nigeria. Breast cancer research and treatment. 2007, 110: 183-188.CrossRefPubMed
19.
go back to reference Al-Kuraya K, Schraml P, Sheikh S, et al.: Predominance of high-grade pathway in breast cancer development of Middle East women. Modern Pathology. 2005, 18: 891-897. 10.1038/modpathol.3800408.CrossRefPubMed Al-Kuraya K, Schraml P, Sheikh S, et al.: Predominance of high-grade pathway in breast cancer development of Middle East women. Modern Pathology. 2005, 18: 891-897. 10.1038/modpathol.3800408.CrossRefPubMed
20.
go back to reference Bin Amer SN, Magbool Z, Nirmal MS, et al.: Gene expression profiling in women with breast cancer in a Saudi population. Saudi Med J. 2008, 29: 507-513.PubMed Bin Amer SN, Magbool Z, Nirmal MS, et al.: Gene expression profiling in women with breast cancer in a Saudi population. Saudi Med J. 2008, 29: 507-513.PubMed
21.
go back to reference Al-Tamimi DM, Bernard PS, Shawarby MA, et al.: Distribution of molecular breast cancer subtypes in Middle Eastern-Saudi Arabian women: A pilot study. Ultrastructural Pathology. 2009, 33: 141-150.CrossRefPubMed Al-Tamimi DM, Bernard PS, Shawarby MA, et al.: Distribution of molecular breast cancer subtypes in Middle Eastern-Saudi Arabian women: A pilot study. Ultrastructural Pathology. 2009, 33: 141-150.CrossRefPubMed
22.
go back to reference Ibrahim EM, al-Mulhim FA, al-Amri A, al-Muhanna FA, Ezzat AA, Stuart RK, Ajarim D: Breast cancer in the Eastern province of Saudi Arabia. Med Oncol. 1998, 15 (4): 241-247. 10.1007/BF02787207.CrossRefPubMed Ibrahim EM, al-Mulhim FA, al-Amri A, al-Muhanna FA, Ezzat AA, Stuart RK, Ajarim D: Breast cancer in the Eastern province of Saudi Arabia. Med Oncol. 1998, 15 (4): 241-247. 10.1007/BF02787207.CrossRefPubMed
23.
go back to reference Ezzat AA, Ibrahim EM, Raja MA, Al-Sobhi S, Rostom A, Stuart RK: Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population. Med Oncology. 1999, 16 (2): 95-103. 10.1007/BF02785842.CrossRef Ezzat AA, Ibrahim EM, Raja MA, Al-Sobhi S, Rostom A, Stuart RK: Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population. Med Oncology. 1999, 16 (2): 95-103. 10.1007/BF02785842.CrossRef
Metadata
Title
Very low prevalence of epidermal growth factor receptor (EGFR) protein expression and gene amplification in Saudi breast cancer patients
Authors
Mohamed A Shawarby
Dalal M Al-Tamimi
Ayesha Ahmed
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2011
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-6-57

Other articles of this Issue 1/2011

Diagnostic Pathology 1/2011 Go to the issue