e17540 Background: The hepatocyte growth factor/MET pathway has been shown to cause tumor progression in several types of carcinomas. We reported that c-Met up-regulated topoisomease I (Topo I) in non-small cell lung cancer cell lines (submitted for publication). The aims of this study were 1) to examine the prognostic influence of c-MET/phospho-MET (p-Met), or Topo I expression and 2) to elucidate correlation between c-Met/p-Met expression and Topo I expression in small cell lung cancer (SCLC). Methods: This retrospective study included 72 SCLC patients (pts) with available tumor tissue from primary lung tumor or metastatic lesions and clinical data including survival. We performed immunohistochemistry to detect c-MET/phospho-MET and Topo I expression. Results: Tumor tissues were obtained from 72 SCLC pts. Sixty-six pts, (51 male, 15 female, median age 67.5 range 43-91, LD/ED 38/28, PS0,1/2,3,4 57/9) were evaluated. c-Met overexpression was seen in 40.9%, p-Met in 74.2%, and Topo I expression in 59.1%, respectively. High expression of Topo I associated with lower response rate (RR) (96.7% in low group vs 78.4% in high group, p=0.029) and shorter progression-free survival (PFS) (65W vs 39W, p=0.040) but did not correlate with overall survival (OS). Phosphorylation of Met protein did not correlate with RR, PFS or OS. Interestingly, intensity of p-Met significantly correlated with Topo I expression (p=0.048). High expression of c-Met protein did not associated with RR or PFS but significantly associated with shorter OS (high 53W, low 95W, p=0.018). Multivariate analysis which included c-Met, stage, PS, and age resulted that c-Met was an independent prognostic factor for OS of pts with SCLC (HR; 2.144, 95% confidence interval 1.162-3.956, p=0.015). Conclusions: This study suggested c-Met high expression was an independent prognostic factor, and Topo I was up-regulated by Met in SCLC.