Meme Kanserinde Ki67 İndeks Ölçümlerinin Manuel ve Dijital Yöntemler Açısından Kıyaslanması

Öz

Amaç: Meme kanserinde immunhistokimyasal biyobelirteç olarak umut vaat eden Ki67 proteini, mitoz döngüsünün tüm aktif fazlarında bulunduğundan hücre proliferasyon değerlendirmelerinde kullanılır. Ki67 indeksi meme kanserli hastalarda prediktif ve prognostik değerdedir. Manuel değerlendirme (MD) ile Ki67 sayımı gözlemciler arası değişkenliğe hassas ve zaman alıcıdır. Son yıllarda, dijital görüntü analizinin (DGA) Ki67 ölçümleri için hızlı ve objektif olduğunu belirten çalışmalar artmaktadır ancak bu yöntemin rutin uygulamaya girmesi ileri çalışmaları gerektirmektedir. Bu araştırmada 85 invaziv meme kanseri vakasında MD, DGA ve GK (göz kararı) Ki67 ölçümlerini kıyaslanmıştır. Yöntem: Tümör moleküler tipleri, mitoz sayıları, GK, MD ve DGA ile ölçülmüş Ki67 değerleri ve korelasyonları saptandı. DGA analizleri ViraPath (Virasoft Yazılım, İstanbul, Türkiye) yazılımıyla, parametreler arasında istatistik korelasyonlar NCSS (Number Cruncher Statistical System, 2020) ile incelendi. Bulgular: Her üç farklı metotla belirlenmiş Ki67 indeks değerlerinin yaş, histolojik derece, mitoz sayıları ve moleküler tip açısından korelasyon ve farklılıkları literatür ile uyumlu bulundu. DGA ve MD ile sayılmış Ki67 indeksleri arasında sınıf içi korelasyon katsayısı 0,974 olarak ölçüldü ve Bland Altman analizleri ile MD ve DGA sayımları arasındaki fark sıfıra yakın saptandı. Sonuç: DGA sayımları MD’nin yerini alacak güvenilirlikte sonuçlar vermektedir. Çok merkezli ve metot standartlarını optimize edecek çalışmalarla patoloji pratiğine zamansal katkı ve yüksek hassasiyet kazandırılabilir.

Anahtar Kelimeler

• Meme kanseri
• Ki67
• manuel sayım
• dijital görüntü analizi

Comparison of Ki67 Index Measurements in Breast Cancer with Manual and Digital Methods

Abstract

Aim: Ki67 protein, which shows promise as an immunohistochemical biomarker in breast cancer, is used in cell proliferation assessments since it is present in all active phases of the mitotic cycle. Ki67 index has predictive and prognostic value in patients with breast cancer. Ki67 counting with manual assessment (MD) is sensitive to interobserver variability and is time consuming. In recent years, studies indicating that digital image analysis (DGA) is fast and objective for Ki67 measurements have been increasing, but the routine application of this method requires further studies. In this study, we compared MD, DGA and GK Ki67 measurements in 85 invasive breast cancer cases. Method: Tumor molecular types, mitotic numbers, Ki67 values measured by GK, MD and DGA and their correlations, were determined. DGA analyses were analyzed with ViraPath (Virasoft Yazılım, Istanbul, Turkey) software, and statistical correlations between parameters were analyzed with NCSS (Number Cruncher Statistical System, 2020). Results: The correlations and differences of Ki67 index values determined by all three different methods in terms of age, histological grade, mitotic numbers, and molecular type were found to be compatible with the international literature. The intraclass correlation coefficient between Ki67 indices counted with DGA and MD was measured as 0.974, and the difference between Bland Altman analysis and MD and DGA counts was found to be close to zero. Conclusion: DGA counts give reliable results to replace MD. With multicenter studies that optimize method standards, time savings and high sensitivity can be brought to the practice of pathology.

Keywords

• Breast Cancer
• Ki67
• manual counting
• digital image analysis

Kaynakça

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