Prognostic significance of Ki-67 immunostaining and symptoms in resected stage I and II non-small cell lung cancer

The proliferative rate of a tumor has been considered predictive of its clinical course. We evaluated the expression of the proliferative marker Ki-67 and its relationship to survival, disease-free survival and other clinicopathologic variables in both stage I and stage II non-small cell lung cancer (NSCLC). A total of 260 patients with surgically resected stage I ( n=193), and II ( n=67) NSCLC with at least 5 years follow-up were identified. The median survival for patients with low expression of Ki-67 (≤25%) was 54 months, while for those with high expression (>25%), it was 45 months ( P=0.1). The disease-free survival in patients with low expression of Ki-67 was 59 months while it was only 32 months for patients with high Ki-67 ( P=0.1). Out of 136 patients, 84 (62%) had both increased S-phase (>8%) and high Ki-67 ( P=0.001). A total of 28 of 30 patients who had loss of antigen A had high expression of Ki-67 (93.3%) ( P=0.03). Ki-67 expression was also higher in squamous cell (54/63, 85.7%) compared to non-squamous cell cancer (70/108, 64%) ( P=0.03). We also analyzed for the presence of symptoms with survival. The presence of symptoms was not found to be statistically significant, for overall survival ( P=0.33) or disease-free survival ( P=0.72). When individual symptoms were analyzed, the presence of cough was statistically significant for both overall and disease-free survival. The median survival was 39 months for patients with cough, and 57 months for patients without cough ( P=0.04). Multivariate analysis showed higher N and T stages, presence of cough and loss of antigen A, predicted for poorer overall survival. Higher N and T stages, loss of antigen A, presence of mucin and cough and increased expression of Ki-67 predicted decreased disease-free survival. Although we did not find a statistically significant difference between low and high Ki-67, there was a trend for a poorer overall and disease-free survival in patients with high Ki-67 expression. Larger studies may be needed to prove a statistically significant effect of Ki-67 on survival. Future studies should assess the potential prognostic significance of the presence of symptoms (particularly cough) in addition to clinical-pathologic variables (such as T and N stage) and biological markers in patients with early stage NSCLC.