PROGNOSTIC IMPACT OF C-MET/PHOSPHO-MET AND TOPOISOMERASE I IN SMALL-CELL LUNG CANCER

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Abstract

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 (i) to examine the prognostic influence of c-MET/phospho-MET (p-Met) or Topo I expression and (ii) 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 carried out immunohistochemistry to detect c-MET/p-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 versus 78.4% in high group, P = 0.029) and shorter progression-free survival (PFS) (65W versus 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.

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