Heparanase and Survivin—potential markers of aggressiveness of colon cancers

Abstract

14524 Background: Survivin is an inhibitor of apoptosis and specifically expressed in several human cancers. Heparanase seems to play an important role in cancer metastasis, angiogenesis and regulation of COX-2 expression. The purpose of this pilot study was to evaluate whether there is a difference in the level of survivin and heparanase expression in paraffin-embedded tissue from patients with colon cancer with and without metastasis. Methods: Paraffin-embedded tissue samples were obtained from 32 patients with primary colon tumors with (n = 15) and without liver metastases (n = 17) at the time of diagnosis. After laser capture microdissection direct quantitative real-time reverse transcriptase PCR (RT-PCR, TaqMan™) assays were performed in triplicates to determine survivin and heparanase gene expression levels. Gene expression was normalized with beta-Actin. Decision tree analysis was used to assess whether higher levels of these genes are associated with the existence of metastasis. Results: Neither survivin nor heparanase gene expression alone showed a significant relationship with the pM-Stage, although the detection levels of heparanase showed a tendency towards significant correlation with the existence of liver metastasis (p = 0.06). Decision tree analysis was used to split patients into two groups based on cut-off values of gene expression most closely associated with the pM-stage. The groupings determined by this analysis were significantly differently correlated with metastasis by Spearman’s test (p=0.03). Conclusions: Our results show that high expression levels of both survivin and heparanase in paraffin- embedded tissue are significantly correlated with the pM-Stage in this patient cohort. In conclusion, using intratumoral survivin and heparanase gene expression levels might be useful to identify patients at risk for liver metastasis. Prospective and larger clinical studies are warranted to validate our preliminary findings. No significant financial relationships to disclose.