Alev OK ATILGAN, Merih TEPEOĞLU, Eda YILMAZ AKÇAY, Leyla HASANALİYEVA, Dalokay KILIÇ, Handan ÖZDEMİR

Müsinöz Olmayan Akciğer Adenokarsinomlarında Caspase-3 ve GRIM-19 Ekspresyonu ile Bu Proteinlerin Klinikopatolojik Önemi

Amaç: Bu çalışmada, müsinöz olmayan akciğer adenokarsinomlarında, apoptotik protein olarak bilinen caspase-3 ve GRIM-19 protein ekspresyonu ve bu proteinlerin klinikopatolojik öneminin araştırılması amaçlandı. Gereç ve Yöntemler: Bu çalışma, 1 Ocak 2010 ile 1 Haziran 2020 tarihleri arasında müsinöz olmayan akciğer adenokarsinomu tanısı alan 81 hasta üzerinde gerçekleştirildi. Caspase-3 ve GRIM-19 ekspresyonlarını incelemek için immünohistokimyasal analiz yapıldı ve bu proteinler ile klinikopatolojik parametreler arasındaki ilişki araştırıldı. Bulgular: Caspase-3 nükleer pozitifliği yüksek dereceli müsinöz olmayan akciğer adenokarsinomlarında daha yaygın bulundu (p<0,001). Caspase-3 sitoplazmik ekspresyonu ileri evre (p=0,021) ve lenf nodu metastazı (p=0,020) olan tümörlerde daha güçlü saptandı. GRIM-19 ekspresyonu, yüksek dereceli müsinöz olmayan akciğer adenokarsinomlu tümörlerde (p=0,002) ve lenfovasküler invazyonlu tümörlerde (p=0,021) düşük idi. Ortanca takip süresi 31,7 (aralık, 1-145) ay idi. Düşük ve yüksek GRIM-19 ekspresyonlu tümörlere sahip hastaların 5 yıllık genel sağkalım oranı sırasıyla %48 ve %92 idi. GRIM-19 ekspresyonu genel 5 yıllık sağkalım oranı üzerinde anlamlı bir etkisi olduğu (p=0,008), ancak 5 yıllık hastalıksız sağkalım oranı üzerinde anlamlı bir etkisi olmadığı (p=0,368) saptandı. Sonuç: Caspase-3 ve GRIM-19 ekspresyonu ile kötü klinikoptolojik özellikler ve prognoz arasında anlamlı bir ilişki olduğunu gösterdik. Literatürde ilk kez, düşük GRIM-19 ekspresyonunun müsinöz olmayan akciğer adenokarsinomunda daha kötü bir klinik gidişle ilişkili olduğunu ortaya koyduk. Caspase-3 ve GRIM-19 müsinöz olmayan akciğer adenokarsinomu hastaları için yeni potansiyel prognostik biyobelirteçlerin yanı sıra potansiyel terapötik hedefler haline gelebilir.

Anahtar Kelimeler:

Apoptosis, Caspase-3, GRIM-19, Akciğer kanseri

The Expression of Caspase-3 and GRIM-19 in Non-mucinous Lung Adenocarcinoma and Their Clinicopathologic Significance

Aim: The current study aimed to investigate apoptotic proteins such as caspase-3 and GRIM-19 protein expression in non-mucinous lung adenocarcinomas and their clinicopathologic significance. Material and Methods: This study was performed on 81 patients diagnosed with non-mucinous lung adenocarcinoma between January 1, 2010, and June 1, 2020. Immunohistochemical analysis was performed to examine the expressions of caspase-3 and GRIM-19, and the association between these proteins and clinicopathological parameters was investigated. Results: Caspase-3 nuclear positivity was more common in high-grade non-mucinous lung adenocarcinomas (p<0.001). Caspase-3 cytoplasmic expression was stronger in tumors with advanced-stage (p=0.021) and lymph node metastases (p=0.020). GRIM-19 expression was low in tumors with high-grade non-mucinous lung adenocarcinomas (p=0.002), and tumors with lymphovascular invasion (p=0.021). The median follow-up time was 31.7 (range, 1-145 months. The overall 5-year survival rate of patients with low and high GRIM-19 expression tumors was 48% and 92%, respectively. GRIM-19 expression significantly affected the 5-year overall survival rate (p=0.008), but not the 5-year disease-free survival rate (p=0.368). Conclusion: We revealed a significant association between caspase-3 and GRIM-19 expressions and poor clinicopathologic features and prognosis. For the first time in the literature, we revealed an association between low GRIM-19 expression and worse clinical outcomes in patients with non-mucinous lung adenocarcinoma. Caspase-3 and GRIM-19 may become potential therapeutic targets and novel potential predictive biomarkers for non-mucinous lung adenocarcinoma patients.

Keywords:

Apoptosis, Caspase-3, GRIM-19, Lung cancer,

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