Prognostic Significance of Apoptotic Index in Completely Resected Non–Small-Cell Lung Cancer

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Abstract
PURPOSE: To evaluate the significance of apoptotic index (AI) as a prognostic factor after surgery for non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 236 patients who underwent surgery for previously untreated pathologic stage I to IIIa NSCLC between 1985 and 1990 were reviewed. AI was defined as the number of apoptotic cells, detected by terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick end-labeling, per 1,000 tumor cells. Proliferative index (PI) and aberrant p53 expression were also evaluated immunohistochemically. RESULTS: The 5-year survival rate for the lowest-AI group (AI < 5.0) was 74.7%; those for the lower-AI group (5.0 ≤ AI < 11.0) and the higher-AI group (11.0 ≤ AI < 25.0) were 51.6% and 57.8%, respectively. These survival rates were significantly lower than that of the lowest-AI group (P = .021 and P = .043, respectively). The highest-AI group (25.0 ≤ AI), however, showed the most favorable prognosis, with a 5-year survival rate of 83.2%. Multivariate analysis confirmed that a moderate AI (5.0 ≤ AI < 11.0 or 11.0 ≤ AI < 25.0) was a significant factor to predict poor prognosis. The PIs for the lowest-, the lower-, the higher-, and the highest-AI groups were 32.3%, 48.0%, 54.3%, and 50.7%, respectively. The lowest-AI group showed a favorable prognosis because of its low PI, whereas the lower- and the higher-AI groups had a poor prognosis caused by increased cancer-cell proliferation. The highest-AI group showed the most favorable prognosis because apoptotic cell death overcame cell proliferation. No significant correlation was observed between AI and aberrant p53 expression. CONCLUSION: AI proved to be an independent prognostic factor in NSCLC.