Orofarengeal skuamöz hücreli karsinomlarda KRAS/BRAF mutasyonunun araştırılması: Bir ön çalışma

Year 2016, Volume: 26 Issue: 5, 265 - 267, 20.10.2016

Ülkü Küçük Ümit Bayol Elif Usturalı Keskin Emel Ebru Pala İbrahim Çukurova Mehmet Ali Çolak Mustafa Değirmenci Özge Özer Altuğ Koç

Abstract

Amaç: Bu çalışmada orofarengeal skuamöz hücreli karsinom OSCC patogenezinde KRAS/BRAF gen mutasyonunun rolü araştırıldı.Hastalar ve Yöntemler: Ocak 2003-Kasım 2013 tarihleri arasında tanısı konan toplam 26 OSCC hastası 23 erkek, 3 kadın; ort. yaş 60 yıl; dağılım 41-77 yıl çalışmaya dahil edildi. Çalışmada KRAS/BRAF mutasyon analizi için kantitatif floresan polimeraz zincir reaksiyonu yöntemi kullanıldı.Bulgular: Tümörlerin 10’u dil kökünde, 12’si bademcikte ve dördü ağız tabanı yerleşimli idi. Ortalama tümör boyutu 3.8 cm idi. Tümörlerin altısı iyi diferansiye, 18’si orta derecede diferansiye ve ikisi kötü diferansiye idi. Tüm olgular KRAS ve BRAF gen mutasyonları için analiz edildi ve bunların hiçbirinde mutasyon saptanmadı.Sonuç: Sınırlı sayıdaki olgu serimizde, OSCC ile KRAS/BRAF gen mutasyonu arasında herhangi bir ilişki saptanamamıştır. Yeni hedefe yönelik tedavi yöntemlerini belirleyebilmek için daha geniş OSCC serilerinde mutasyonun rolü araştırılmalıdır

Keywords

BRAF, KRAS, orofarengeal, skuamöz hücreli karsinom

Investigating KRAS/BRAF mutation in oropharyngeal squamous cell carcinomas: a preliminary study

Abstract

Objectives: This study aims to investigate the role of KRAS/BRAF gene mutation in the pathogenesis of oropharyngeal squamous cell carcinoma OSCC . Patients and Methods: A total of 26 OSCC patients 23 males, 3 females; mean age 60 years; range 41 to 77 years diagnosed between January 2003 and November 2013 were included in the study. The methods used in our study were quantitative fluorescence polymerase chain reaction for KRAS/BRAF mutation analysis. Results: Ten of the tumors were located at the tongue base, 12 in the tonsil and four at the floor of mouth. The mean tumor size was 3.8 cm. Six of the tumors were well differentiated, 18 were moderately differentiated and two were poorly differentiated. All cases were analyzed for KRAS and BRAF gene mutations and none of them showed gene mutations. Conclusion: We could not find any relation between OSCC and KRAS/BRAF gene mutations in our short case file. The role of mutations should be analyzed in larger series in OSCC to predict new targeted therapy modalities.

Keywords

BRAF, KRAS, oropharyngeal, squamous cell carcinoma

References

• Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol 2004;31:744-54.
• Bissada E, Abboud O, Abou Chacra Z, Guertin L, Weng X, Nguyen-Tan PF, et al. Prevalence of K-RAS Codons 12 and 13 Mutations in Locally Advanced Head and Neck Squamous Cell Carcinoma and Impact on Clinical Outcomes. Int J Otolaryngol 2013;2013:848021.
• Spencer JM, Kahn SM, Jiang W, DeLeo VA, Weinstein IB. Activated ras genes occur in human actinic keratoses, premalignant precursors to squamous cell carcinomas. Arch Dermatol 1995;131:796-800.
• McDonald JS, Jones H, Pavelic ZP, Pavelic LJ, Stambrook PJ, Gluckman JL. Immunohistochemical detection of the H-ras, K-ras, and N-ras oncogenes in squamous cell carcinoma of the head and neck. J Oral Pathol Med 1994;23:342-6.
• Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature 2002;417:949-54.
• Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. Int J Cancer 2005;114:806-16.
• De Carvalho TG, De Carvalho AC, Maia DC, Ogawa JK, Carvalho AL, Vettore AL. Search for mutations in signaling pathways in head and neck squamous cell carcinoma. Oncol Rep 2013;30:334-40.
• Langer CJ. Exploring biomarkers in head and neck cancer. Cancer 2012;118:3882-92.
• Smilek P, Neuwirthova J, Jarkovsky J, Dusek L, Rottenberg J, Kostrica R, et al. Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas. Neoplasma 2012;59:508-15.
• Weber A, Langhanki L, Sommerer F, Markwarth A, Wittekind C, Tannapfel A. Mutations of the BRAF gene in squamous cell carcinoma of the head and neck. Oncogene 2003;22:4757-9.
• Van Damme N, Deron P, Van Roy N, Demetter P, Bols A, Van Dorpe J, et al. Epidermal growth factor receptor and K-RAS status in two cohorts of squamous cell carcinomas. BMC Cancer 2010;10:189.
• Bruckman KC, Schönleben F, Qiu W, Woo VL, Su GH. Mutational analyses of the BRAF, KRAS, and PIK3CA genes in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:632-7.
• Friedland P, Thomas A, Naran A, Amanuel B, Grieu- Iacopetta F, Carrello A, et al. Human papillomavirus and gene mutations in head and neck squamous carcinomas. ANZ J Surg 2012;82:362-6.
• Fujii S, Uryu H, Akashi K, Suzuki K, Yamazaki M, Tahara M, et al. Clinical significance of KRAS gene mutation and epidermal growth factor receptor expression in Japanese patients with squamous cell carcinoma of the larynx, oropharynx and hypopharynx. Int J Clin Oncol 2013;18:454-63.