A Significant Study on EGFR Mutations in Lung Carcinomas
Keywords:
lung, cancer, Epidermal, growth, factor
Abstract
BACKGROUND Lung cancer is one of the leading causes of cancer related deaths among both men and women. Non-small cell lung carcinomas comprises the majority (about 75%) of lung cancers, has proven difficult to treat due to poorly understood pathological mechanism. Recent advances in cell signalling pathways that control cell survival have identified genetic and regulatory aberrations that suppress cell death, promote cell division and induce tumorogenesis. One such discovery is that of epidermal growth factor receptor. Overexpression of EGFR has been reported and implicated in pathogenesis of many human malignancies including Non- small cell carcinoma of lung. AIMS AND OBJECTIVES To study EGFR expression by immunohistochemistry in diagnosed cases of Non- small cell carcinomas of lung at our institute. To determine the value of EGFR test by IHC in predicting response to targeted therapy and clinical outcome. MATERIALS AND METHODS A retrospective and prospective study of bronchial biopsies diagnosed as Non-small cell carcinoma for a duration of two years with their expression to EGFR immunohistochemistry marker at our institute and these patients response to the targeted therapy. RESULTS Out of twenty nine (29) cases of lung malignancies majority were Non -small cell carcinomas- twenty seven cases (27), of which adenocarcinomas were seventeen (17) cases topped the list, followed by squamous cell carcinomas (5) cases, malignant epithelial lesions (3) cases and poorly differentiated carcinomas(2) cases. Small cell carcinomas were two (2) cases. Fifteen cases of non- small cell carcinomas cases showed EGFR mutations and twelve patients were started on the targeted therapy of Gefitinib and Erlonitib. All twelve of them showed good response to chemotherapy. CONCLUSIONS Most of the Non-small cell carcinomas of lung have EGFR mutations especially all adenocarcinomas in non-smokers. The clinical outcome of patients could be predicted. There is significant response to targeted chemotherapy.References
1.Jemal A, Thomas A, Murray T, Thun M. Cancer stastics,2002.;52:23-47.
2.Sasaki H, Endo K, Okuda K, Kawano O, Kitahara N, Tanaka H, et al. Epidermal growth factor receptor gene amplification and gefitinib senstivity in patients with recurrent lung cancer.J Cancer Res Clin Oncol.2008;134:469-77.
3.Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al.Comparison of four chemotherapy regimens for advanced non-small lung cancer. N Engl J Med.2002;346:92-8. 4.Ohsaki Y, Tanno S, Fujita Y, Toyoshima E, Fujiuchi S, Nishigaki Y, et al. Epidermal growth receptor expression correlates with poor prognosis in non-small lung cancer patients with p53 overexpression.Oncol Rep.2000;7:603-
5.Paez JG,Janne PA,LeeJC,Tracy S,Greulich H,et al,2004 EGFR mutations in lung cancer:Correlation with clinical response to gefitinib therapy.Science 304:1497-1500.
6.Lynch TJ, Bell DW, Sordella R, Okimoto RA, et al. Activating mutations in the epidetmal growth factor receptor underlying responsiveness of non small cell cancer to gefitinib. N Engl J med 350;2129-2139
7.Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2014; 136: E359-E386.
8. Crinò L, Weder W, van Meerbeeck J and Felip E. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5: v103-v115.
9.Youlden DR, Cramb SM and Baade PD. The International Epidemiology of Lung Cancer: geographical distribution and secular trends. J Thorac Oncol 2008; 3: 819-831.
10. Dearden S, Stevens J, Wu YL and Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap).
11.Lynch TJ,Bell DW,Sordell R, Gurubhagavatula S,Brannigan BW,et al.Activating mutation in the epiderma growth factor recetor underlying responsiveness of non small cell lung cancer to gefitinib.N Engl J Med .2004;350:2129-39.
12.Paez JG, Janne PA, Lee JC ,Tracy S,Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science .2004;12:6494-501.
13.Pao w,miller V, Zakowski M, Doherty J, Politi K,et al.(2004) EGF receptor gene mutations are common in lung cancers from never smokers and are associated with sensitivity of tumours to gefitinib nd erlotinib,Proc Natl Acad Sci USA 101:13306-13311
14.Sartori G,Cavazza A,Sgambato A,Marchioni A,Barbieri F,Lucia Longo,et al.EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors.Am J clinc pathol.2009;131:478-89
15.Ninomiya H,Hiramatsu M,Inamura K et al.Correlation between morphology and EGFR mutations in lung adenocarcinoma;significance of the micropapillary pattern and hobnail cell type.Lung cancer.2009:63;235-40
2.Sasaki H, Endo K, Okuda K, Kawano O, Kitahara N, Tanaka H, et al. Epidermal growth factor receptor gene amplification and gefitinib senstivity in patients with recurrent lung cancer.J Cancer Res Clin Oncol.2008;134:469-77.
3.Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al.Comparison of four chemotherapy regimens for advanced non-small lung cancer. N Engl J Med.2002;346:92-8. 4.Ohsaki Y, Tanno S, Fujita Y, Toyoshima E, Fujiuchi S, Nishigaki Y, et al. Epidermal growth receptor expression correlates with poor prognosis in non-small lung cancer patients with p53 overexpression.Oncol Rep.2000;7:603-
5.Paez JG,Janne PA,LeeJC,Tracy S,Greulich H,et al,2004 EGFR mutations in lung cancer:Correlation with clinical response to gefitinib therapy.Science 304:1497-1500.
6.Lynch TJ, Bell DW, Sordella R, Okimoto RA, et al. Activating mutations in the epidetmal growth factor receptor underlying responsiveness of non small cell cancer to gefitinib. N Engl J med 350;2129-2139
7.Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2014; 136: E359-E386.
8. Crinò L, Weder W, van Meerbeeck J and Felip E. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5: v103-v115.
9.Youlden DR, Cramb SM and Baade PD. The International Epidemiology of Lung Cancer: geographical distribution and secular trends. J Thorac Oncol 2008; 3: 819-831.
10. Dearden S, Stevens J, Wu YL and Blowers D. Mutation incidence and coincidence in non small-cell lung cancer: meta-analyses by ethnicity and histology (mutMap).
11.Lynch TJ,Bell DW,Sordell R, Gurubhagavatula S,Brannigan BW,et al.Activating mutation in the epiderma growth factor recetor underlying responsiveness of non small cell lung cancer to gefitinib.N Engl J Med .2004;350:2129-39.
12.Paez JG, Janne PA, Lee JC ,Tracy S,Greulich H, Gabriel S, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science .2004;12:6494-501.
13.Pao w,miller V, Zakowski M, Doherty J, Politi K,et al.(2004) EGF receptor gene mutations are common in lung cancers from never smokers and are associated with sensitivity of tumours to gefitinib nd erlotinib,Proc Natl Acad Sci USA 101:13306-13311
14.Sartori G,Cavazza A,Sgambato A,Marchioni A,Barbieri F,Lucia Longo,et al.EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors.Am J clinc pathol.2009;131:478-89
15.Ninomiya H,Hiramatsu M,Inamura K et al.Correlation between morphology and EGFR mutations in lung adenocarcinoma;significance of the micropapillary pattern and hobnail cell type.Lung cancer.2009:63;235-40
Published
2019-06-24
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