Baş-Boyun Skuamöz Hücreli Karsinomlarında EGFR, P16 ve Ki67 Ekspresyonunun Prognoza Etkisi

Öz

Amaç: EGFR ve HPV pozitif baş-boyun kanserlerinin, negatif olanlara kıyasla oldukça farklı klinik ve demografik özelliklerinden dolayı HPV ve EGFR ekspresyon durumu bağımsız prognostik faktör olarak kullanılabilir. Bu çalışmanın amacı baş-boyun skuamöz hücreli karsinom vakalarında EGFR, p16 ve ki67 ekspresyonlarının yaşam süresi ile ilişkisini saptamaktır.

Materyal ve Metot: Çalışmaya baş-boyun yerleşimli 47 orta derecede diferansiye skuamöz hücreli karsinom olgusu alındı. Olgulara immünohistokimya ile EGFR, p16 ve ki67 çalışıldı. Bu belirteçlerin yaşam süresiyle ilişkisi değerlendirildi.

Bulgular: Olguların 14’ü (%29,7) EGFR ekspresyonu göstermiş, 33’ünde (%70,3) boyanma görülmemiştir. Olguların 21’inde (%44,6) p16 ile boyanma görülmüş, 26’sında (%55,4) p16 ekspresyonu görülmemiştir. Hastaların ortalama takip süresi 32 aydır. 47 hastanın 15’i hastalık sebebiyle ex olmuştur. Yaşayan ve ex olan hastaların ki67 proliferasyon indeksi arasındaki fark istatistiksel olarak anlamlıdır (p=0,037). EGFR pozitif olan hastaların yaşam süresi, negatif olanlara göre anlamlı olarak daha kısadır (p=0,037). Ortalama sağkalım p16 pozitif 20 hastada 30 ay, p16 negatif hastalarda 33.5 ay idi (p=0,847).

Sonuç: Çalışmamız EGFR ve ki67’nin baş-boyun skuamöz hücreli karsinom hastalarında prognoz ve sağkalımı öngörmek için önemli bir belirteç olabileceğini desteklemektedir.  

Anahtar Kelimeler

• baş&boyun skuamöz hücreli karsinom
• EGFR
• p16
• ki67
• prognoz

The Effect of EGFR, P16 and Ki67 Expression on Prognosis in Head and Neck Squamous Cell Carcinoma

Öz

Objective: HPV and EGFR expression status may be utilized as an independent prognostic factor owing to the different clinical and demographic characteristics head and neck cancers. In the study, it was aimed to investigate the association between EGFR, p16 and ki67 expression and survival in patients with head and neck squamous cell carcinoma (SCC).

Materials and Methods: A total of 43 patients with SCC of the head and neck region were included in the study. EGFR, p16 and Ki67 were examined by means of immunohistochemistry. The association between these markers and survival was investigated.

Results: EGFR expression was detected in 14 cases (32.5%), Staining with p16 was positive in 20 cases (46.5%). Mean duration of follow up was 32 months. There was a statistically significant difference between ki67 proliferation indices of patients who survived and those who died (p=0.037). Survival was significantly shorter in EGFR positive patients compared to those negative for EGFR expressions (p=0.037). Mean survival was 30 months in the 20 p16 positive patients and 33.5 months in p16 negative patients (p=0.847).

Conclusion: This study supports that EGFR and Ki67 may be important markers to predict prognosis and survival in patients with head and neck SCC. 

Anahtar Kelimeler

• head and neck squamous cell carcinoma
• EGFR
• p16
• Ki67
• prognosis

Kaynakça

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893-2917.
2. Argyris PP, Slama Z, Malz C, et al. Intracellular calprotectin (S100A8/A9) controls epithelial differentiation and caspase-mediated cleavage of EGFR in head and neck squamous cell carcinoma. Oral Oncology. 2019;95:1-10.
3. Sivasithamparam J, Visk CA, Cohen EE, King AC. Modifiable risk behaviors in patients with head and neck cancer. Cancer. 2013;119:2419-2426.
4. Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics. CA Cancer J Clin. 2016;66:271-289.
5. Maxwell SA, Sacks PG, Gutterman JU, Gallick GE. Epidermal growth factor receptor protein-tyrosine kinase activity in human cell lines established from squamous carcinomas of the head and neck. Cancer Res. 1989;49(5):1130-1137.
6. Bossi P, Resteghini C, Paielli N, Licitra L, Pilotti S, Perrone F. Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma. Oncotarget. 2016;7(45):74362-74379.
7. Almadori G, Cadoni G, Cattani P, et al. Human papillomavirus infection and epidermal growth factor receptor expression in primary laryngeal squamous cell carcinoma. Clin Cancer Res. 2001;7:3988-3993.
8. Vermorken JB, Mesia R, Rivera F, et al. Platinumbased chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116-1127.

9. Mesía R, Henke M, Fortin A, et al. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015;16:208-220.
10. Giralt J, Trigo J, Nuyts S, et al. Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015;16:221-232.
11. Gioacchini FM, Alicandri‑Ciufelli M, Magliulo G, Rubini C, Presutti L, Re M. The clinical relevance of Ki‑67 expression in laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2015;272:1569-1576.
12. Maebayashi T, Ishibashi N, Aizawa T, et al. Roles of Ki-67 and p16 as biomarkers for unknown primary head and neck squamous cell carcinoma. European Archives of Oto-Rhino-Laryngology. 2019;276:1221-1229.
13. Kontic M, Colovic Z, Paladin I, Mirko Gabelica, Baric A, Pesutic-Pisac V. Association between EGFR expression and clinical outcome of laryngeal HPV squamous cell carcinoma. Acta Oto-Laryngologıca. 2019;139(10):913-917.
14. Oguejiofor KK, Hall JS, Mani N, et al. The prognostic significance of the biomarker p16 in oropharyngeal squamous cell carcinoma. clinical oncology. 2013;25:630-638.
15. Kontic M, Milovanovic J, Colovic Z, et al. Epidermal growth factor receptor (EGFR) expression in patients with laryngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2015;272:401-405.
16. Poeta ML, Manola J, Goldwasser MA, et al. TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med. 2007;357:2552-2561.
17. Perrone F, Suardi S, Pastore E, et al. Molecular and cytogenetic subgroups of oropharyngeal squamous cell carcinoma. Clin Cancer Res. 2006;12:6643-6651.
18. Liu H, Zhang B, Sun Z. Spectrum of EGFR aberrations and potential clinical implications: insights from integrative pan-cancer analysis. Cancer Communications. 2020;40:43-59.
19. Nagalakshmi K, Jamil K, Rani PU. Polymorphism in EGFR gene and its association in head and neck cancer patients with tobacco and alcohol consuming habits. New Frontiers in Medicine and Medical Research. 2021;9:152-161.
20. Stanek L, Glendova K, Tesarova P, et al. Molecular and IHC analysis of head and neck carcinomas associated with HPV infection. Bratisl Med J. 2019;120(11):832-838.
21. Wang F, Zhang H, Xue Y, et al. A systematic investigation of the association between HPV and the clinicopathological parameters and prognosis of oral and oropharyngeal squamous cell carcinomas. Cancer Medicine. 2017;6(5):910-917.