1Pulmonologist, Lung Diseases Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2Pathologist, Cancer Molecular Pathology Research Center, Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3Resident of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Ir
4Pulmonologist, Cardio-Thoracic Surgery & Transplant Research Center, Emam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
5Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Introduction: Growth, proliferation, survival, and differentiation are the prominent characteristics of cells, which are affected by cancer. Epidermal growth factor receptor (EGFR) plays a pivotal role in the effective control of these features. Given the significance of EGFR signaling pathway in non-small cell lung cancer (NSCLC), EGFR expression is influential on these cell characteristics. In this paper, we studied EGFR expression and its association with demographic factors, clinicopathological features, and prognosis of NSCLC patients. Materials and Methods: In this retrospective cohort study which was done during 2009-12 at Ghaem Hospital, Mashhad, Iran. EGFR expression was evaluated in 96 patients with formalin-fixed, paraffin-embedded NSCLC tissues (43 adenocarcinomas, 48 squamous-cell carcinomas, and 5 large-cell carcinomas) using immunohistochemistry (IHC). Data analysis was performed by SPSS version 20.0. Results: Out of 96 specimens, approximately 53% were classified as positive for EGFR expression. The study group consisted of 68% (N=65) male and 32% (N=31) female subjects, with the mean age of 61.1±9.03 years. There was no difference between EGFR-positive and EGFR-negative patients in terms of the overall survival rate (P=0.49). In addition, no association was observed between tumor histology and EGFR expression (P=0.08), while EGFR-positive adenocarcinoma (N=28, 29%) was more prevalent compared to other subtypes of NSCLC. Moreover, there were no differences between tumor subtypes and the overall survival rate of the patients (P=0.21), and no association was found between EGFR expression and the patients’ demographic factors (e.g. age and gender). Conclusion: The results of this study indicated that EGFR expression could not be a prognostic marker in NSCLC patients; however, it seems that using standardized IHC scoring is likely to yield more reliable data in this regard.
Horn L, Pao W, Johnson DH. Neoplasms of the lung. In: Harrison's principles of internal medicine [Internet]. 18 th ed. U.S: The McGraw-Hill Companies, Inc; 2012.
Suh JH. Current Readings: Pathology, Prognosis, and Lung Cancer. Semin Thorac Cardiovasc Surg. 2013;25:14-21.
Teh E, Belcher E. Lung cancer: diagnosis, staging and treatment. Surgery (Oxford). 2014;32:242-8.
Edwin F, Wiepz GJ, Singh R, Peet CR, Chaturvedi D, Bertics PJ, et al. A Historical Perspective of the EGF Receptor and Related Systems. Methods Mol Biol. 2006; 327:1-24.
Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005;5:341-54.
Hanahan D, Weinberg Robert A. Hallmarks of Cancer: The Next Generation. Cell. 2011; 144: 646-74.
Figueroa-Magalhães MC, Jelovac D, Connolly RM, Wolff AC. Treatment of HER2-positive breast cancer. The Breast. 2014;23:128-36.
Savonarola A, Palmirotta R, Guadagni F, Silvestris F. Pharmacogenetics and pharmacogenomics: role of mutational analysis in anti-cancer targeted therapy. Pharmacogenomics J. 2012;12:277-86.
Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7:169-81.
Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, 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;350:2129-39.
Reck M, Heigener DF, Mok T, Soria J-C, Rabe KF. Management of non-small-cell lung cancer: recent developments. The Lancet. 2013;382:709-19.
Ettinger DS, Akerley W, Bepler G, Blum MG, Chang A, Cheney RT, et al. Non-small cell lung cancer clinical practice guidelines in oncology.. J Natl Compr Canc Netw. 2006;4:548.
Johnson DH, Schiller JH, Bunn PA. Recent Clinical Advances in Lung Cancer Management. J Clin Oncol. 2014;32:973-82.
Reck M, Popat S, Reinmuth N, De Ruysscher D, Kerr KM, Peters S. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014; 25 (Suppl 3):iii27-39
Meert A-P, Martin B, Delmotte P, Berghmans T, Lafitte J-J, Mascaux C, et al. The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis. Eur Respir J. 2002;20:975-81.
Selvaggi G, Novello S, Torri V, Leonardo E, De Giuli P, Borasio P, et al. Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung cancer. Ann Oncol. 2004;15:28-32.
Niemiec J, Kołodziejski L, Dyczek S, Gasińska A. Prognostic significance of epidermal growth factor receptor in surgically treated squamous cell lung cancer patients. Folia Histochem Cytobiol. 2004;42:111-8.
Ludovini V, Bellezza G, Pistola L, Bianconi F, Di Carlo L, Sidoni A, et al. High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients. Ann Oncol. 2009;20:842-9.
Gately K, Forde L, Cuffe S, Cummins R, Kay EW, Feuerhake F, et al. High Coexpression of Both EGFR and IGF1R Correlates With Poor Patient Prognosis in Resected Non–Small-Cell Lung Cancer. Clin Lung Cancer. 2014;15:58-66.
Dacic S, Flanagan M, Cieply K, Ramalingam S, Luketich J, Belani C, et al. Significance of EGFR Protein Expression and Gene Amplification in Non–Small Cell Lung Carcinoma. Am J Clin Pathol. 2006; 125:860-5.
Moreira AL, Mino-Kenudson M. Update on histologic classification of non-small cell lung cancer. Diagn Histopathol. 2014; 20:385-91.
Ahn J-H, Kim S-W, Hong S-M, Suh C, Kim WK, Lee IC, et al. Epidermal growth factor receptor (EGFR) expression in operable non-small cell lung carcinoma. J Korean Med Sci. 2004;19:529-35.
Dazzi H, Hasleton PS, Thatcher N, Barnes DM, Wilkes S, Swindell R, et al. Expression of epidermal growth factor receptor (EGF-R) in non-small cell lung cancer. Use of archival tissue and correlation of EGF-R with histology, tumour size, node status and survival. Br J Cancer. 1989;59:746-9.
Rusch V, Klimstra D, Venkatraman E, Pisters PW, Langenfeld J, Dmitrovsky E. Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin Cancer Res. 1997; 3: 515-22.
Pfeiffer P, Nexø E, Bentzen SM, Clausen PP, Andersen K, Rose C. Enzyme-linked immunosorbent assay of epidermal growth factor receptor in lung cancer: comparisons with immunohistochemistry, clinicopathological features and prognosis. Br J Cancer. 1998;78:96-9.
Jeon YK, Sung SW, Chung JH, Park WS, Seo JW, Kim CW, et al. Clinicopathologic features and prognostic implications of epidermal growth factor receptor (EGFR) gene copy number and protein expression in non-small cell lung cancer. Lung Cancer. 2006; 54:387-98.
Hirsch FR, Varella-Garcia M, Bunn PA, Di Maria MV, Veve R, Bremnes RM, et al. Epidermal Growth Factor Receptor in Non–Small-Cell Lung Carcinomas: Correlation Between Gene Copy Number and Protein Expression and Impact on Prognosis. J Clin Oncol. 2003;21:3798-807.