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 OJPathology  Vol.2 No.4 , October 2012
Overexpression of Her1 (EGFR) in Gastric Cancer: A Saudi Regional Population Based Study
Abstract: Background: Gastric cancer is one of the commonest malignant tumor worldwide. Its treatment remains a challenge for physicians. Epidermal growth factor receptor (EGFR) inhibitors have played a significant role in the management of solid malignancies including colorectal cancer. In this study we aimed to determine EGFR expression in gastric adenocarcinoma by standardized immunohistochemistry in a Saudi regional population based cohort and also to evaluate Ki-67 proliferating index and p-53 mutation status. Materials and Methods: Gastric carcinoma (GC) cases comprising surgical resection specimens and endoscopic biopsies, were selected, from the pathology archives of King Fahd Hospital of the University of Dammam (KFHU), spanning a time period of 6 years. The histological GC type was delineated according to Laurens classification and immunohistochemical (IHC) protein analysis for EGFR, Ki-67 and p-53 was carried out. Results: 42 cases of gastric GC were analyzed and EGFR overexpression was demonstrated in 4.76% of cases. Out of these 2.38% had membranous and the remaining demonstrated predominantly cytoplasmic along with focal membranous positivity. Ki-67 proliferation index ranged from moderate to high and p-53 mutation status was negative in these cases. Conclusion: Low EGFR expressivity could be reflective of regional variation in cancer characteristics. The study also highlights the inadequacy of the currently employed gastric EGFR interpretation criterions and stresses on development of standardized and uniform EGFR evaluation protocols tailored for gastric needs.
Cite this paper: A. Ahmed and D. M. Al Tamimi, "Overexpression of Her1 (EGFR) in Gastric Cancer: A Saudi Regional Population Based Study," Open Journal of Pathology, Vol. 2 No. 4, 2012, pp. 120-126. doi: 10.4236/ojpathology.2012.24022.
References

[1]   D. P. Kelsen, et al.,“Adjuvant and Neoadjuvant Therapy for Gastric Cancer,” Seminars in Oncology, Vol. 23, No. 3, 1996, pp. 379-389.

[2]   D. M. Parkin, P. Pisani and J. Ferlay, “Estimates of the Worldwide Incidence of Eighteen Major Cancers in 1985,” International Journal of Cancer, Vol. 54, No. 4, 1993, pp. 594-606. doi:10.1002/ijc.2910540413

[3]   D. A. Corley and P. A. Buffler, “Oesophageal and Gastric Cardia Adenocarcinomas: Analysis of Regional Variation Using the Cancer Incidence in Five Continents Database,” International Journal of Epidemiology, Vol. 30, No. 6, 2001, pp. 1415-1425. doi:10.1093/ije/30.6.1415

[4]   B. Hermann, R. Dietrich and A. Volker, “Epidemiology of Stomach Cancer,” Springer Protocols, Vol. 472, 2008, pp. 467-477.

[5]   D. M. Parkin, F. Bray, J. Ferlay and P. Pisani, “Estimating the World Cancer Burden: Globocan 2000,” International Journal of Cancer, Vol. 94, No. 2, 2001, pp. 153-156. doi:10.1002/ijc.1440

[6]   A. Jemal, et al., “Cancer Statistics, 2008,” Cancer Journal for Clinicians, Vol. 58, No. 2, 2008, pp. 71-96. doi:10.3322/CA.2007.0010

[7]   A. Ohtsu, “Chemotherapy for Metastatic Gastric Cancer: Past, Present, and Future,” Journal of Gastroenterology, Vol. 43, No. 4, 2008, pp. 256-264. doi:10.1007/s00535-008-2177-6

[8]   C. S. Fuchs and R. J. Mayer, “Gastric Carcinoma,” The New England Journal of Medicine, Vol. 333, No. 1, 1995, pp. 32-41. doi:10.1056/NEJM199507063330107

[9]   Z. Liang, et al., “Analysis of EGFR,HER2, and TOP2A Gene Status and Chromosomal Polysomy in Gastric Adenocarcinoma from Chinese Patients,” BMC Cancer, Vol. 8, 2008, p. 363. doi:10.1186/1471-2407-8-363

[10]   D. A. Corley and P. A. Buffler, “Oesophageal and Gastric Cardia Adenocarcinomas: Analysis of Regional Variation Using the Cancer Incidence in Five Continents Database,” International Journal of Epidemiology, Vol. 30, No. 6, 2001, pp. 1415-1425. doi:10.1093/ije/30.6.1415

[11]   T. Takehana, et al., “Status of c-erbB-2 in Gastric Adenocarcinoma: A Comparative Study of Immunohisto-chemistry, Fluorescence in Situ Hybridization and Enzyme-Linked Immuno-Sorbent Assay,” International Journal of Cancer, Vol. 98, No. 6, 2002, pp. 833-837. doi:10.1002/ijc.10257

[12]   L. Albarello, et al., “HER2 Testing in Gastric Cancer.” Advances in Anatomic Pathology, Vol. 18, No. 1, 2011, pp. 53-59. doi:10.1097/PAP.0b013e3182026d72

[13]   “Cetuximab Approved by FDA for Treatment of Head and Neck Squamous Cell Cancer,” Cancer Biology & Therapy, Vol. 5, No. 4, 2006, pp. 340-342.

[14]   R. M. Giusti, et al., “FDA Drug Approval Summary: Panitumumab (Vectibix),” Oncologist, Vol. 12, No. 5, 2007, pp. 577-583. doi:10.1634/theoncologist.12-5-577

[15]   M. H. Cohen, et al., “FDA Drug Approval Summary: Erlotinib (Tarceva) Tablets,” Oncologist, Vol. 10, No. 7, 2005, pp. 461-466. doi:10.1634/theoncologist.10-7-461

[16]   P. Laurent-Puig and J. Taieb, “Lessons from Tarceva in Pancreatic Cancer: Where Are We Now, and How Should Future Trials Be Designed in Pancreatic Cancer?” Current Opinion in Oncology, Vol. 20, No. 4, 2008, pp. 454-458. doi:10.1097/CCO.0b013e32830218d6

[17]   M. V. Karamouzis, et al., “Therapies Directed against Epidermal Growth Factor Receptor in Aerodigestive Carcinomas,” Journal of the American Medical Association, Vol. 298, No. 1, 2007, pp. 70-82. doi:10.1001/jama.298.1.70

[18]   A. Gon?alves, et al., “A Polymorphism of EGFR Extracellular Domain Is Associated with Progression Free-Survival in Metastatic Colorectal Cancer Patients Receiving Cetuximab-Based Treatment,” BMC Cancer, Vol. 8, 2008, p. 169. doi:10.1186/1471-2407-8-169

[19]   P. Lauren, “The Two Histological Main Types of Gastric Carcinoma: Diffuse and so Called Intestinal Type Carcinoma. An Attempt at a Histo-Clinical Classification,” Acta Pathol Microbiol Scand, Vol. 64, 1965, pp. 31-49.

[20]   T. Braut, et al., “Epidermal Growth Factor Receptor Protein Expression and Gene Amplification in Normal, Hyperplastic, and Cancerous Glottic Tissue: Immunohisto-chemical and Fluorescent in Situ Hybridization Study on Tissue Microarrays,” Croatian Medical Journal, Vol. 50, No. 4, 2009, pp. 370-379. doi:10.3325/cmj.2009.50.370

[21]   R. Bhargava, et al., “EGFR Gene Amplification in Breast Cancer: Correlation with Epidermal Growth Factor Receptor mRNA and Protein Expression and HER-2 Status and Absence of EGFR-Activating Mutations,” Modern Pathology, Vol. 18, No. 8, 2005, pp. 1027-1033. doi:10.1038/modpathol.3800438

[22]   C. G. Kleer, et al., “Pathologic, Immunohistochemical, and Molecular Features of Benign and Malignant Phyllodes Tumors of the Breast,” Modern Pathology, Vol. 14, No. 3, 2008, pp. 185-190. doi:10.1038/modpathol.3880282

[23]   T. Dragovich and C. Campen, “Anti-EGFR-Targeted Therapy for Esophageal and Gastric Cancers: An Evolving Concept,” Journal of Oncology, Vol. 2009, 2009, Article ID: 804108. doi:10.1155/2009/804108

[24]   E. Mammano, et al., “Epidermal Growth Factor Receptor (EGFR): Mutational and Protein Expression Analysis in Gastric Cancer,” Anticancer Research, Vol. 26, No. 5A, 2006, pp. 3547-3350.

[25]   T. Takehana, et al., “Expression of Epidermal Growth Factor Receptor in Gastric Carcinomas,” Clinical Gastroenterology and Hepatology, Vol. 1, No. 6, 2003, pp. 438-445. doi:10.1016/S1542-3565(03)00219-2

[26]   J. W. Lee, et al., “Absence of EGFR Mutation in the Kinase Domain in Common Human Cancers Besides Non-Small Cell Lung Cancer,” International Journal of Cancer, Vol. 113, No. 3, 2005, pp. 510-511. doi:10.1002/ijc.20591

[27]   K. Mimori, et al., “The Epidermal Growth Factor Receptor Gene Sequence Is Highly Conserved in Primary Gastric Cancers,” Journal of Surgical Oncology, Vol. 93, No. 1, 2006, pp. 44-46. doi:10.1002/jso.20426

[28]   G. Galizia, et al., “Epidermal Growth Factor Receptor (EGFR) Expression Is Associated with a Worse Prognosis in Gastric Cancer Patients Undergoing Curative Surgery,” World Journal of Surgery, Vol. 31, No. 7, 2007, pp. 1458-1468. doi:10.1007/s00268-007-9016-4

[29]   J. G. Paez, et al., “EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy,” Science, Vol. 304, No. 5676, 2004, pp. 1497-1500. doi:10.1126/science.1099314

[30]   H. J. Lee, et al., “Protein Overexpression and Gene Amplification of Epidermal Growth Factor Receptor in Non Small Cell Lung Carcinomas: Comparison of Four Commercially Available Antibodies by Immunohisto-chemistry and Fluorescence in Situ Hybridization Study,” Lung Cancer, Vol. 68, No. 3, 2010, pp. 375-382. doi:10.1016/j.lungcan.2009.07.014

[31]   M. Hofmann, et al., “Assessment of a HER2 Scoring System for Gastric Cancer: Results from a Validation Study,” Histopathology, Vol. 52, No. 7, 2008, pp. 797-805. doi:10.1111/j.1365-2559.2008.03028.x

[32]   S. C. Wang and M. C. Hung, “Cytoplasmic/Nuclear Shuttling and Tumor Progression,” Annals of the New York Academy of Sciences, Vol. 1059, 2005, pp. 11-15. doi:10.1196/annals.1339.002

[33]   S. Y. Lin, et al., “Nuclear Localization of EGF Receptor and Its Potential New Role as a Transcription Factor,” Nature Cell Biology, Vol. 3, No. 9, 2001, pp. 802-808. doi:10.1038/ncb0901-802

[34]   H. W. Lo, et al., “Nuclear Interaction of EGFR and STAT3 in the Activation of the iNOS/NO Pathway,” Cancer Cell, Vol. 7, No. 6, 2005, pp. 575-589. doi:10.1016/j.ccr.2005.05.007

[35]   Lo HW, et al., “EGFR Signaling Pathway in Breast Cancers: From Traditional Signal Transduction to Direct Nuclear Translocalization,” Breast Cancer Research and Treatment, Vol. 95, No. 3, 2006, pp. 211-218. doi:10.1007/s10549-005-9011-0

[36]   J. S. de Bono and E. K. Rowinsky, “The ErbB Receptor Family: A Therapeutic Target for Cancer,” Trends in Molecular Medicine, Vol. 8, No. 4, 2002, pp. S19-S26. doi:10.1016/S1471-4914(02)02306-7

[37]   J. P. Kallio, et al., “Membranous Location of EGFR Immunostaining Is Associated with Good Prognosis in Renal Cell Carcinoma,” British Journal of Cancer, Vol. 89, No. 7, 2003, pp. 1266-1269. doi:10.1038/sj.bjc.6601241

[38]   C. Langner, et al., “Are Heterogenous Results of EGFR Immunoreactivity in Renal Cell Carcinoma Related to Non-Standardised Criteria for Staining Evaluation?” Journal of Clinical Pathology, Vol. 57, No. 7, 2004, pp. 773-775. doi:10.1136/jcp.2003.015743

[39]   G. C. Li, et al., “Are Biomarkers Correlated with Recurrence Patterns in Patients with Resectable Gastric Adenocarcinoma,” Molecular Biology Reports, Vol. 39, No. 1, 2012, pp. 399-405. doi:10.1007/s11033-011-0751-0

[40]   N. E. Hynes and H. A. Lane, “ERBB Receptors and Cancer: The Complexity of Targeted Inhibitors,” Nature Reviews Cancer, Vol. 5, No. 5, 2005, pp. 341-354. doi:10.1038/nrc1609

[41]   V. W. Lui, J. R. Grandis, “EGFR-Mediated Cell Cycle Regulation,” Anticancer Research, Vol. 22, No. 1A, 2002, pp. 1-11.

[42]   Tumor Research Center, “The Expression of p53, PCNA, EGFR and Its Relationship to Clinicopathological Features and Prognosis of Gastric Cancer.” http://www.tumorres.com/tumor-biol/37091.htm

[43]   Y. Maehara, et al., “Prognostic Value of p53 Protein Expression for Patients with Gastric Cancer—A Multivariate Analysis,” British Journal of Cancer, Vol. 79, No. 7-8, 1999, pp. 1255-1261. doi:10.1038/sj.bjc.6690201

[44]   X. P. Liu, et al., “Combined Examination of p27(Kip1), p21(Waf1/Cip1) and p53 Expression Allows Precise Estimation of Prognosis in Patients with Gastric Carcinoma,” Histopathology, Vol. 39, No. 6, 2001, pp. 603-610. doi:10.1046/j.1365-2559.2001.01283.x

[45]   M. S. Al-Moundhri, et al., “The Prognostic Significance of p53, p27 kip1, p21 waf1, HER-2/Neu, and Ki67 Proteins Expression in Gastric Cancer: A Clinicopathological and Immunohistochemical Study of 121 Arab Patients,” Journal of Surgical Oncology, Vol. 91, No. 4, 2005, pp. 243-252. doi:10.1002/jso.20324

[46]   K. Motojima, et al., “Expression of p53 Protein in Gastric Carcinomas Is Not Independently Prognostic,” Surgery, Vol. 116, No. 5, 1994, pp. 890-895.

[47]   H. E. Gabbert, et al., “The Relationship of p53 Expression to the Prognosis of 418 Patients with Gastric Carcinoma,” Cancer, Vol. 76, No. 5, 1995, pp. 720-726. doi:10.1002/1097-0142(19950901)76:5<720::AID-CNCR2820760503>3.0.CO;2-E

[48]   V. W. Lui and J. R. Grandis, “EGFR-Mediated Cell Cycle Regulation,” Anticancer Research, Vol. 22, No. 1A, 2002, pp. 1-11.

[49]   E. Tahara, “Genetic Pathways of Two Types of Gastric Cancer,” IARC Scientific Publications, Vol. 157, 2004, pp. 327-349.

 
 
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