Hilal ÖZAKINCI, Serpil DİZBAY SAK, Malahat MUSAYEVA, Şenay BOYACIGİL, Öznur COŞKUN

Küçük hücreli dışı akciğer karsinomlu Türk hastalarda epidermal büyüme faktör reseptör mutasyonları ve tiroid transkripsiyon faktör-1 durumunun değerlendirilmesi: Tek merkezli 600 hastalık çalışma

Amaç: Bu çalışmada küçük hücreli dışı akciğer kanserli Türk topolumunda epidermal büyüme faktör reseptör mutasyonlarının sıklığı, dağılımı ve morfolojik/immünhistokimyasal özellikleri araştırıldı ve materyal tipi ve mutasyon analizinin teknik başarısı arasındaki muhtemel ilişki incelendi. Çalışma planı: Eylül 2012 - Aralık 2015 tarihleri arasında Sanger sekanslama yöntemi ile epidermal büyüme faktör reseptör mutasyon testi yapılan, daha önce tedavi edilmemiş, primer veya metastatik küçük hücreli dışı akciğer kanserli toplam 499 ardışık hasta (437 erkek, 163 kadın; ort. yaş 61 yıl; dağılım, 30-84 yıl) retrospektif olarak incelendi. Arşiv kayıtları ve hematoksilen-eozin ve immünohistokimya boyalı kesitler yeniden değerlendirildi. Doku array bloklarında tiroid transkripsiyon faktör-1 ve napsin A immünohistokimyasal boyamaları yapıldı. Bulgular: Yetmiş hastada (%14) 75 mutasyon saptandı. Sitolojik materyallerde analizin başarı oranı ve intakt deoksiribonükleik asit parça uzunluğu, doku materyallerine kıyasla, anlamlı olarak daha yüksekti (p

Evaluation of epidermal growth factor receptor mutations and thyroid transcription factor-1 status in Turkish non-small cell lung carcinoma patients: A study of 600 cases from a single center

Background: This study aims to investigate the frequency, distribution,and morphological/immunohistochemical features of epidermal growthfactor receptor mutations and to examine the possible relationshipbetween the material type and technical success of mutation analysis inTurkish population with non-small cell lung cancer.Methods: Between September 2012 and December 2015, a total of499 consecutive, treatment-naïve patients (437 males, 163 females;mean age 61 years; range, 30 to 84 years) with primary or metastaticnon-small cell lung cancer who underwent epidermal growth factorreceptor mutation testing using Sanger sequencing method wereretrospectively analyzed. Archival records and hematoxylin-eosine andimmunohistochemically stained sections were re-examined. The thyroidtranscription factor-1 and napsin A immunohistochemical stains wereperformed on tissue array blocks.Results: Seventy-five mutations were detected in 70 patients (14%).The success rate of testing and intact deoxyribonucleic acid fragmentlength were significantly higher in the cytological material, comparedto tissue specimens (p

PDF

___

1. Lai Y, Zhang Z, Li J, Sun D, Zhou Y, Jiang T, et al. EGFR mutations in surgically resected fresh specimens from 697 consecutive Chinese patients with non-small cell lung cancer and their relationships with clinical features. Int J Mol Sci 2013;14:24549-59.
2. Sun PL, Seol H, Lee HJ, Yoo SB, Kim H, Xu X, et al. High incidence of EGFR mutations in Korean men smokers with no intratumoral heterogeneity of lung adenocarcinomas: correlation with histologic subtypes, EGFR/TTF-1 expressions, and clinical features. J Thorac Oncol 2012;7:323-30.
3. Papadopoulou E, Tsoulos N, Tsirigoti A, Apessos A, Agiannitopoulos K, Metaxa-Mariatou V, et al. Determination of EGFR and KRAS mutational status in Greek non-smallcell lung cancer patients. Oncol Lett 2015;10:2176-84.
4. Ozluk Y, Firat P, Yegen G, Hocaoglu J, Tas S, Yilmazbayhan D. EGFR mutation testing using archivalstained smears in non-small cell lung carcinoma. Cytopathology 2017;28:35-45.
5. Skov BG, Høgdall E, Clementsen P, Krasnik M, Larsen KR, Sørensen JB, et al. The prevalence of EGFR mutations in non-small cell lung cancer in an unselected Caucasian population. APMIS 2015;123:108-15.
6. Chen Z, Liu X, Zhao J, Yang H, Teng X. Correlation of EGFR mutation and histological subtype according to the IASLC/ ATS/ERS classification of lung adenocarcinoma. Int J Clin Exp Pathol 2014;7:8039-45.
7. Ninomiya H, Hiramatsu M, Inamura K, Nomura K, Okui M, Miyoshi T, et al. Correlation between morphology and EGFR mutations in lung adenocarcinomas Significance of the micropapillary pattern and the hobnail cell type. Lung Cancer 2009;63:235-40.
8. Szumera-Ciećkiewicz A, Olszewski WT, Tysarowski A, Kowalski DM, Głogowski M, Krzakowski M, et al. EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish, single institution study and systematic review of European incidence. Int J Clin Exp Pathol 2013;6:2800-12.
9. Cetin Z, Ozbilim G, Erdogan A, Luleci G, Karauzum SB. Evaluation of PTEN and Mcl-1 expressions in NSCLC expressing wild-type or mutated EGFR. Med Oncol 2010;27:853-60.
10. Baykara O, Tansarikaya M, Demirkaya A, Kaynak K, Tanju S, Toker A, et al. Association of epidermal growth factor receptor and K-Ras mutations with smoking history in non-small cell lung cancer patients. Exp Ther Med 2013;5:495-8.
11. Akca H, Demiray A, Yaren A, Bir F, Koseler A, Iwakawa R, et al. Utility of serum DNA and pyrosequencing for the detection of EGFR mutations in non-small cell lung cancer. Cancer Genet 2013;206:73-80.
12. Unal OU, Oztop I, Calibasi G, Baskin Y, Koca D, Demir N, et al. Relationship between epidermal growth factor receptor gene mutations and clinicopathological features in patients with non-small cell lung cancer in western Turkey. Asian Pac J Cancer Prev 2013;14:3705-9.
13. Sag SO, Gorukmez O, Ture M, Gorukmez O, Deligonul A, Sahinturk S, et al. Spectrum of EGFR gene mutations and ALK rearrangements in lung cancer patients in Turkey. Springerplus 2016;5:482.
14. 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;31:87.
15. Dogan M, Demirkazik A, Tukun A, Sak SD, Ceyhan K, Yalcin B, et al. The Relationship Between Common EGFR, BRAF, KRAS Mutations and Prognosis in Advanced Stage Non-Small Cell Lung Cancer with Response to the Treatment in Turkey. UHOD 2014;24:1-10.
16. Kus T, Aktas G, Sevinc A, Kalender ME, Yilmaz M, Kul S, et al. Prognostic impact of initial maximum standardized uptake value of (18)F-FDG PET/CT on treatment response in patients with metastatic lung adenocarcinoma treated with erlotinib. Onco Targets Ther 2015;8:3749-56.
17. Kanmaz ZD, Aras G, Tuncay E, Bahadır A, Kocatürk C, Yaşar ZA, et al. Contribution of 18Fluorodeoxyglucose positron emission tomography uptake and TTF-1 expression in the evaluation of the EGFR mutation in patients with lung adenocarcinoma. Cancer Biomark 2016;16:489-98.
18. Güler Tezel G, Şener E, Aydın Ç, Önder S. Prevalence of epidermal growth factor receptor mutations in patients with non-small cell lung cancer in turkish population. Balkan Med J 2017;34:567-71.
19. Lee JG, Kim S, Shim HS. Napsin A is an independent prognostic factor in surgically resected adenocarcinoma of the lung. Lung Cancer 2012;77:156-61.
20. Jie-Liu, Li XY, Zhao YQ, Liu RQ, Zhang JB, Ma J, et al. Genotype-phenotype correlation in Chinese patients with pulmonary mixed type adenocarcinoma: Relationship between histologic subtypes, TITF-1/SP-A expressions and EGFR mutations. Pathol Res Pract 2014;210:176-81.
21. Arrieta O, Cardona AF, Martín C, Más-López L, Corrales- Rodríguez L, Bramuglia G, et al. Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). J Thorac Oncol 2015;10:838-43.
22. Lu F, Li S, Dong B, Zhang S, Lv C, Yang Y. Identification of lung adenocarcinoma mutation status based on histologic subtype: Retrospective analysis of 269 patients. Thorac Cancer 2016;7:17-23.
23. Leichsenring J, Volckmar AL, Magios N, Morais de Oliveira CM, Penzel R, Brandt R, et al. Synonymous EGFR variant p.Q787Q is neither prognostic nor predictive in patients with lung adenocarcinoma. Genes Chromosomes Cancer 2017;56:214-20.
24. Lee GH, Choi YM, Kim JM, Shin JJ, Kim JG, Moon SY. Association of epidermal growth factor receptor gene polymorphisms with advanced endometriosis in a Korean population. Eur J Obstet Gynecol Reprod Biol 2012;164:196-9.
25. Sasaki H, Endo K, Takada M, Kawahara M, Tanaka H, Kitahara N, et al. EGFR polymorphism of the kinase domain in Japanese lung cancer. J Surg Res 2008;148:260-3.