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Nuclear Localization of Apoptosis Protease Activating Factor-1 Predicts Survival after Tumor Resection in Early-Stage Non–Small Cell Lung Cancer

¹ Institut Gustave Roussy, Division of Cancer Medicine, Villejuif, France; ² Commissariat de l’Energie Atomique, Laboratoire de Radiobiologie et Oncologie, Fontenay aux Roses, France; ³ Centre National de la Recherche Scientifique-Unité mixte de Recherche 8125, Institut Gustave Roussy, Villejuif, France; ⁴ Department of Medical Oncology, Pitié Salpetrière Hospital, Paris, France; ⁵ Avicenne Hospital, Avicenne Hospital, Bobigny, France

ABSTRACT

The proapoptotic protein apoptosis protein activating factor-1 (Apaf-1), which is normally located in the cytoplasm, can translocate to the nucleus before non-small cell lung carcinoma (NSCLC) cells manifest signs of apoptosis such as mitochondrial damage, caspase activation, or chromatin condensation. This may indicate a stage of imminent apoptosis. Importantly, we found that 24% (15 of 62) of resected stage I NSCLC (T₁N₀M₀ or T₂N₀M₀), manifested a marked nuclear localization of Apaf-1 (Apaf-1^Nuc), as compared with the mostly cytoplasmic localization of Apaf-1 found in the remaining tumors (Apaf-1^Cyt). After a median follow-up of 6.31 years, the actuarial 5-year overall survival rates were 89% (56–98%) in the Apaf-1^Nuc group and 54% (36–71%) in the Apaf-1^Cyt group (P = 0.039). No correlation between the subcellular localization of Apaf-1 and that of p53 and Hsp70 could be established. Thus, the subcellular location of Apaf-1 (but not that of p53 or Hsp70) constitutes an accurate prognostic factor for overall survival in NSCLC.

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