Int J Med Sci 2018; 15(10):1025-1034. doi:10.7150/ijms.25734 This issue
1. Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Ishikawa.
2. Department of Thoracic Surgery, Kanazawa Medical University, Ishikawa.
3. Department of Pathology, Kanazawa Medical University Hospital, Ishikawa.
4. Division of Molecular Cell Biology, Department of Biomolecular Sciences, Saga University Faculty of Medicine, Saga, Japan.
Background: Oxidative stress plays pivotal roles in the progression of lung adenocarcinoma (LUAD) through cell signaling related closely to cancer growth. We previously reported that peroxiredoxin 4 (PRDX4), a secretory-type antioxidant enzyme, can protect against the development of various diseases, including potential malignancies. Since many patients with early-stage LUAD develop recurrence, even after curative complete resection, we investigated the association of the PRDX4 expression with the clinicopathological features and recurrence/prognosis using post-surgical samples of stage I-LUAD.
Methods: The expression of PRDX4 and MIB-1, a widely accepted Ki67 protein, was immunohistochemically analysed in 206 paraffin-embedded tumour specimens of patients with stage I-LUAD. The PRDX4 expression was considered to be weak when less than 25% of the adenocarcinoma cells showed positive staining.
Results: A weak PRDX4+ expression demonstrated a significantly close relationship with pathologically poor differentiation, highly invasive characteristics and recurrence. The decrease in PRDX4-positivity potentially induced cell growth in LUAD, which was correlated significantly with a very high MIB-1 labelling index (≥17.3%). Univariate/multivariate analyses revealed that the subjects with both weak PRDX4+ expression and a very high MIB-1 index had significantly worse disease-free survival rates than other subjects.
Conclusions: The combination of weak PRDX4 expression and a very high MIB-1 index can predict high proliferating activity and recurrence with a potential poor prognosis, especially in post-operative stage I-LUAD patients.
Keywords: lung adenocarcinoma (LUAD), stage I, PRDX4, MIB-1, recurrence.