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EGFR and KRAS mutations in Turkish non-small cell lung cancer patients: a pilot study

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Abstract

EGFR and KRAS mutation profile in non-small cell lung cancers (NSCLCs) shows wide variations due to geographic and ethnic background. We aimed to determine the frequency and types of EGFR and KRAS mutations in a sample group of Turkish NSCLC cases. The study included 14 adenocarcinomas (ACs), 11 squamous cell carcinoma (SCC) patients selected from archival material including small biopsy or surgical specimens. Their formalin fixed paraffin-embedded tumor tissues were used for genomic DNA extraction for EGFR exon 19 and 21, and KRAS exon 2 mutations. Eleven NSCLCs (44 %) had EGFR mutations. Exon 19 and 21 mutations were found in 8 (32 %) and 5 (20 %) cases. Two cases showed double EGFR mutations. In ACs, 5 (35.7 %) patients had EGFR gene mutation, 3 in exon 19 and 3 in exon 21. In SCCs, 6 (54.5 %) cases had EGFR mutation, 5 in exon 19 and 2 in exon 21. All exon 19 mutations were deletion-type mutations. For exon 21, 3 cases had L858R point mutation (CTG>CGG) and two cases showed deletion-type mutations. Six (24 %) NSCLCs showed KRAS mutations (three ACC, three SCC), 5 codon 12 mutations (G>T, T>C, G>A) and one codon 13 mutation (G>T). Three NSCLC cases showed both EGFR and KRAS mutations together. The profile of KRAS mutation in our AC cases was quite similar to those seen in the Western countries; however, frequency and clustering of EGFR mutations were similar to those seen in the Eastern countries.

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References

  1. Yamamoto H, Toyooka S, Mitsudomi T. Impact of EGFR mutation analysis in non-small cell lung cancer. Lung Cancer. 2009;63:315–21.

    Article  PubMed  Google Scholar 

  2. Cheng L, Zhang S, Alexander R, et al. The landscape of EGFR pathways and personalized management of non-small-cell lung cancer. Future Oncol. 2011;7:519–41.

    Article  CAS  PubMed  Google Scholar 

  3. Inamura K, Ninomiya H, Ishikawa Y, et al. Is the epidermal growth factor receptor status in lung cancers reflected in clinicopathologic features? Arch Pathol Lab Med. 2010;134:66–72.

    CAS  PubMed  Google Scholar 

  4. Mitsudomi T, Yatabe Y. Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J. 2010;277:301–8.

    Article  CAS  PubMed  Google Scholar 

  5. 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. PNAS. 2004;101:13306–11.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Suda K, Tomizawa K, Mitsudomi T. Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation. Cancer Metastasis Rev. 2010;29:49–60.

    Article  CAS  PubMed  Google Scholar 

  7. 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;350:2129–39.

    Article  CAS  PubMed  Google Scholar 

  8. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–500.

    Article  CAS  PubMed  Google Scholar 

  9. Dacic S. EGFR assays in lung cancer. Adv Anat Pathol. 2008;15:241–7.

    Article  CAS  PubMed  Google Scholar 

  10. Lee CK, Brown C, Gralla RJ, et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2013;105:595–605.

    Article  CAS  PubMed  Google Scholar 

  11. Garassino MC, Marsoni S, Floriani I. Testing epidermal growth factor receptor mutations in patients with non-small-cell lung cancer to choose chemotherapy: the other side of the coin. J Clin Oncol. 2011;29:3835–7.

    Article  PubMed  Google Scholar 

  12. Tanaka T, Matsuoka M, Sutani A, et al. Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer. 2010;126:651–5.

    Article  CAS  PubMed  Google Scholar 

  13. Liu Y, Xu ML, Zhong HH, et al. EGFR mutations are more frequent in well-differentiated than in poor-differentiated lung adenocarcinomas. Pathol Oncol Res. 2008;14:373–9.

    Article  CAS  PubMed  Google Scholar 

  14. Bae NC, Chae MH, Lee MH, et al. EGFR, ERBB2, and KRAS mutations in Korean non-small cell lung cancer patients. Cancer Genet Cytogenet. 2007;173:107–13.

    Article  CAS  PubMed  Google Scholar 

  15. Li M, Zhang Q, Liu L, et al. The different clinical significance of EGFR mutations in exon 19 and 21 in non-small cell lung cancer patients of China. Neoplasma. 2011;58:74–81.

    Article  CAS  PubMed  Google Scholar 

  16. Blons H, Cote JF, Le Corre D, et al. Epidermal growth factor receptor mutation in lung cancer are linked to bronchioloalveolar differentiation. Am J Surg Pathol. 2006;30:1309–15.

    Article  PubMed  Google Scholar 

  17. Na II, Rho JK, Choi YJ, et al. Clinical features reflect exon sites of EGFR mutations in patients with resected non-small-cell lung cancer. J Korean Med Sci. 2007;22:393–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Brandao GDA, Brega EF, Spatz A. The role of molecular pathology in non-small-cell lung carcinoma—now and in the future. Curr Oncol. 2012;19:S24–32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Mitsudomi T, Yatabe Y. Mutations of the epidermal growth factor receptor gene and related genes as determinants of epidermal growth factor receptor tyrosine kinase inhibitors sensitivity in lung cancer. Cancer Sci. 2007;98:1817–24.

    Article  CAS  PubMed  Google Scholar 

  20. Ladanyi M, Pao W. Lung adenocarcinoma: guiding EGFR-targeted therapy and beyond. Mod Pathol. 2008;21:S16–22.

    Article  CAS  PubMed  Google Scholar 

  21. Riely GJ, Marks J, Pao W. KRAS mutations in non-small cell lung cancer. Proc Am Thorac Soc. 2009;6:201–5.

    Article  CAS  PubMed  Google Scholar 

  22. Riely GJ, Kris MG, Rosenbaum D, et al. Frequency and distinctive spectrum of KRAS mutations in never smokers with lung adenocarcinoma. Clin Cancer Res. 2008;14:5731–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Wu CC, Hsu HY, Liu HP, et al. Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications. Cancer. 2008;113:3199–208.

    Article  CAS  PubMed  Google Scholar 

  24. Wang Z, Wu YL, Zhang GC, et al. EGFR/KRAS mutations and gefitinib therapy in Chinese NSCLC patients. Onkologie. 2008;31:174–8.

    Article  PubMed  Google Scholar 

  25. Massarelli E, Varella-Garcia M, Tang X, et al. KRAS mutation is an important predictor of resistance to therapy with epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. Clin Cancer Res. 2007;13:2890–6.

    Article  CAS  PubMed  Google Scholar 

  26. Park SH, Ha SY, Lee JI, et al. Epidermal growth factor receptor mutations and the clinical outcome in male smokers with squamous cell carcinoma of lung. J Korean Med Sci. 2009;24:448–52.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Finberg KE, Sequist LV, Joshi VA, et al. Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features. J Mol Diagn. 2007;9:320–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Remon J, Morán T, Majem M, et al. Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: a new era begins. Cancer Treat Rev. 2014;40:93–101.

    Article  CAS  PubMed  Google Scholar 

  29. Guan JL, Zhong WZ, An SJ, et al. KRAS mutation in patients with lung cancer: a predictor for poor prognosis but not for EGFR-TKIs or chemotherapy. Ann Surg Oncol. 2013;20:1381–8.

    Article  PubMed  Google Scholar 

  30. Linardou H, Dahabreh IJ, Kanaloupiti D, et al. Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 2008;9:962–72.

    Article  CAS  PubMed  Google Scholar 

  31. Schmid K, Oehl N, Wrba F, et al. EGFR/KRAS/BRAF mutations in primary lung adenocarcinomas and corresponding locoregional lymph node metastases. Clin Cancer Res. 2009;15:4554–60.

    Article  CAS  PubMed  Google Scholar 

  32. Jürgens J, Engel-Riedel W, Prickartz A, et al. Combined point mutation in KRAS or EGFR genes and EML4-ALK translocation in lung cancer patients. Future Oncol. 2014;10:529–32.

    Article  PubMed  Google Scholar 

  33. Masago K, Fujita S, Mio T, et al. Accuracy of epidermal growth factor receptor gene mutation analysis by direct sequencing method based on small biopsy specimens from patients with non-small cell lung cancer: analysis of results in 19 patients. Int J Clin Oncol. 2008;13:442–6.

    Article  CAS  PubMed  Google Scholar 

  34. Warth A, Penzel R, Brandt R, et al. Optimized algorithm for Sanger sequencing-based EGFR mutation analyses in NSCLC biopsies. Virchows Arch. 2012;460:407–14.

    Article  CAS  PubMed  Google Scholar 

  35. Solomon SB, Zakowski MF, Pao W, et al. Core needle lung biopsy specimens: adequacy for EGFR and KRAS mutational analysis. Am J Roentgenol (AJR). 2010;194:266–9.

    Article  Google Scholar 

  36. Lim EH, Zhang SL, Yu K, et al. An alternative approach to determining therapeutic choices in advanced non-small cell lung carcinoma (NSCLC): maximizing the diagnostic procedure and the use of low-volume lung biopsies. J Thorac Oncol. 2007;2:387–96.

    Article  PubMed  Google Scholar 

  37. Cheung YC, Chang JW, Hsieh JJ, et al. Adequacy and complications of computed tomography-guided core needle biopsy on non-small cell lung cancers for epidermal growth factor receptor mutations demonstration: 18-gauge or 20-gauge biopsy needle. Lung Cancer. 2010;67:166–9.

    Article  PubMed  Google Scholar 

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Conflict of interest

All the authors declare that no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, Suleyman Demirel University, Isparta, Turkey

    Sema Bircan

  2. Department of Pathology, Anadolu Medical Center, Gebze, Turkey

    Huseyin Baloglu

  3. Department of Pathology, Gulhane Medical Academy Haydarpasa Teaching Hospital, Istanbul, Turkey

    Zafer Kucukodaci

  4. Department of Chest Disease, School of Medicine, Suleyman Demirel University, Isparta, Turkey

    Ahmet Bircan

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  1. Sema Bircan
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  2. Huseyin Baloglu
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  4. Ahmet Bircan
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Correspondence to Sema Bircan.

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Bircan, S., Baloglu, H., Kucukodaci, Z. et al. EGFR and KRAS mutations in Turkish non-small cell lung cancer patients: a pilot study. Med Oncol 31, 87 (2014). https://doi.org/10.1007/s12032-014-0087-4

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  • DOI: https://doi.org/10.1007/s12032-014-0087-4

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