There is only limited data on the prevalence of epidermal growth factor receptor (EGFR) activating mutations in squamous cell carcinomas and adenosquamous carcinomas of the lung in patients of the Southern Bulgarian region and the efficacy of EGFR tyrosine kinase inhibitors. AIM: Previous reports for Bulgarian population showed high incidence of EGFR mutations in the squamous cell carcinomas, so we set the goal to investigate their frequency in Southern Bulgaria, after precise immunohistochemical verification of lung cancers. MATERIALS AND METHODS: Two hundred and thirty-six lung carcinomas were included in this prospective study. All biopsies were initially analysed with p63, TTF1, Napsin A, CK7, CK34βE12, synaptophysin, CK20 and CDX2. Two hundred and twenty-five non-small cell lung carcinomas were studied with real-time PCR technology to assess the status of the EGFR gene. RESULTS: We detected 132 adenocarcinomas (58.7%), 89 squamous cell carcinomas (39.2%), 4 adenosquamous carcinomas (1.8%), 9 large cell neuroendocrine carcinomas (3.8%) and 2 metastatic colorectal adenocarcinomas (0.8%). Activating mutations in the EGF receptor had 3 out of 89 squamous cell carcinomas (3.37%). We have established mutations in L858R, deletion in exon 19 and rare mutation in S7681. One out of four adenosquamous carcinomas had a point mutation in the L858R (25%). CONCLUSIONS: The frequency of EGFR mutations we found in lung squamous cell carcinomas in a Southern Bulgarian region is lower than that in European countries. Ethnic diversity in the region does not play role of an independent predictive factor in terms of mutation frequency.
1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61(2):69-90.
2. Kim HS, Mitsudomi T, Soo RA, Cho BC. Personalized therapy on the horizon for squamous cell carcinoma of the lung. Lung Cancer 2013;80(3):249-55.
3. Giaccone G. Epidermal growth factor receptor inhibitors in the treatment of non-small-cell lung cancer. J Clin Oncol 2005;23(14):3235-42.
4. Kwak EL, Bang YJ, Camidge DR, Shaw AT, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363(18):1693-703.
5. Scagliotti GV, Parikh P, von Pawel, J Biesma B, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapynaive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26(21):3543-51.
6. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2004;22(11):2184-91.
7. Shiozawa T, Ishii G, Goto K, Nagai K, et al. Clinicopathological characteristics of EGFR mutated adenosquamous carcinoma of the lung. Pathol Int 2013;63(2):77-84.
8. Damjanov D, Koinov K, Naseva E, Bichev St. Frequency of activating EGFR mutations in patients with non-small-cell lung cancer in Bulgaria and treatment with gefi tinib. J Bulg Cancer Society 2013;9(1):28-32 (Bulgarian).
9. Damjanov D. Gefitinib in the treatment of non-smallcell- lung cancer in patients with EGFR positive mutation status. J Bulg Cancer Society 2012;8(1):4-8 (Bulgarian).
10. Fiala O, Pesek M, Finek J, Benesova L, et al. Gene mutations in squamous cell NSCLC: insignificance of EGFR, KRAS and PIK3CA mutations in prediction of EGFR-TKI treatment effi cacy. Anticancer Res 2013;33(4):1705-11.
11. Miyamae Y, Shimizu K, Hirato J, Araki T, et al. Significance of epidermal growth factor receptor gene mutations in squamous cell lung carcinoma Oncol Rep 2011;25(4):921-8.
12. Baik CS, Pritchard CC, Eaton KD, Chow LQ. EGFR mutations in squamous cell lung cancer in neversmokers. J Thorac Oncol 2013;8(1):e6-7.
13. Sasaki H, Endo K, Yukiue H, Kobayashi Y, et al. Mutation of epidermal growth factor receptor gene in adenosquamous carcinoma of the lung. Lung Cancer 2007;55(1):129-30.
14. Toyooka S, Yatabe Y, Tokumo M, Ichimura K, et al. Mutations of epidermal growth factor receptor and K-ras genes in adenosquamous carcinoma of the lung. Int J Cancer 2006;118(6):1588-90.
15. Kang SM, Kang HJ, Shin JH, Kim H, et al. Identical epidermal growth factor receptor mutations in adenocarcinomatous and squamous cell carcinomatous components of adenosquamous carcinoma of the lung. Cancer 2007;109(3):581-7.
16. Jia XL, Chen G. EGFR and KRAS mutations in Chinese patients with adenosquamous carcinoma of the lung. Lung Cancer 2011;74(3):396-400.
17. Wang R, Pan Y, Li C, Zhang H, et al. Analysis of major known driver mutations and prognosis in resected adenosquamous lung carcinomas. J Thorac Oncol 2014;9(6):760-8.
18. Bircan S, Baloglu H, Kucukodaci Z, Bircan A. EGFR and KRAS mutations in Turkish non-small cell lung cancer patients: a pilot study. Med Oncol 2014;31(8):87.
19. Powrózek T, Krawczyk P, Ramlau R, Sura S, et al. EGFR gene mutations in patients with adenosquamous lung carcinoma. Asia Pac J Clin Oncol 2014;10(4):340-5.
20. Blons H, Côté JF, Le Corre D, Riquet M, et al. Epidermal growth factor receptor mutation in lung cancer are linked to bronchioloalveolar differentiation. Am J Surg Pathol 2006;30(10):1309-15.
21. Tokumo M, Toyooka S, Kiura K, Shigematsu H, et al. The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers. Clin Cancer Res 2005;11(3):1167-73.
22. Iwanaga K, Sueoka-Aragane N, Nakamura T, et al. The long-term survival of a patient with adenosquamous lung carcinoma harboring EGFR-activating mutations who was treated with gefitinib. Intern Med 2012;51(19):2771-4.
23. Paik PK, Varghese AM, Sima CS, Moreira AL, et al. Response to erlotinib in patients with EGFR mutant advanced non-small cell lung cancers with a squamous or squamous like component. Intern Med 2012;51(19):2771-4.
24. Liam CK, Leow HR, Pang YK. EGFR mutation testing for squamous cell lung carcinoma. Letters to the Editor. J Thorac Oncol 2013;8(12):e114.
25. Maemondo M, Inoue A, Kobayashi K, Sugawara S, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010;362(25):2380-8.
26. Shukuya T, Takahashi T, Kaira R, Ono A, et al. Efficacy of gefitinib for non-adenocarcinoma nonsmall- cell lung cancer patients harboring epidermal growth factor receptor mutations: a pooled analysis of published reports. N Engl J Med 2010;362(25): 2380-8.