PO-302 The role of SPARCL1 in upper urinary tract cancer of Taiwan

Abstract

IntroductionUpper urinary tract urothelial carcinoma (UTUC) in Taiwan is a relatively high prevalent cancer and locally advanced UTUC often carries a poor prognosis. This study is to analyse role of SPARCL1 in UTUC of Taiwan and analyse if there were any association between SPARCL1 presentation and clinical oncologic outcome.Material and methodsWe initially got fresh frozen cancer tissue from three high grade locally advanced UTUC (stage >2) and three fresh frozen normal urothelium tissue from low grade and stage 0 disease in Kaohsiung Chang Gung Memorial Hospital. In this study, we used DNA methylation assay and SPARCL1 was identified as most significant different DNA methylation in locally advanced cancer compared with normal urothelium tissue. From 2005 to 2012, this study included 78 patients with pT3N0M0 UTUC. Perioperative factors, pathological features, and SPARCL1 immunostaining were reviewed and prognostic factors were examined by multivariate analysis. Cell line study with BFTC909 and BFTC909-SPARCL1 overexpression was used for cancer behaviour observation. The sensitivity of both cell line to cisplatin and radiation was tested.Results and discussionsSPARCL1 was revealed as 20 fold change of methylation in locally advanced UTUC compared with normal urothelium. The patient demography revealed that all pT3N0M0 patient is each group have similar clinical and pathological factors. Systemic UTUC recurrence was significant more in UTUC with negative SPARCL1 presentation (p=0.042). Multivariate analysis found that negative SPARCL1 and non-papillary tumour architexture were the two significant prognostic factors associated with systemic UTUC recurrence (p=0.011 and 0.008 respectively). Cell line study revealed that BFTC 909-SPARCL1 overexpression is associated with less aggressive cancer cell migration/invasion and more sensitivity to cisplatin or radiation treatment.ConclusionSPARCL1 is the most significant methylated gene in locally advanced tissue compared with normal urothelium. For those patients with pT3N0M0 UTUC, SPARCL1 is an independent prognostic marker. The presence of SPARCL1 interferes with UTUC cell line behaviour and sensitivity to cisplatin or radiation.