SPARC in pancreatic cancer: Results from the CONKO-001 study.

Abstract

4016 Background: Previous investigations in pancreatic cancer suggested an important prognostic role for SPARC (secreted protein acidic and rich in cysteine) expression in the peritumoral stroma but not for cancer-cell cytoplasmic SPARC expression. So far no data from prospective studies in patients after curatively intended surgery are available. Methods: CONKO-001, a prospective randomized phase III study, investigated the role of adjuvant gemcitabine as compared to observation. Tissue samples of 160 patients were collected and analysed by immunohistochemistry for the expression of SPARC in the peritumoral stroma (strong versus not strong [=moderate to negative]) and in the tumor cell cytoplasm (immunoreactive score IRS 0-12, 0-2 = negative, 3-12 = positive) by a pathologist blinded to clinical outcome. Kaplan-Meier analyses for disease-free survival (DFS) and overall survival (OS) were performed in dependence of SPARC expression. Results: Strong stromal SPARC expression was associated with worse DFS and OS in the overall study population (strong vs not-strong DFS 9.0 vs 12.6 months, p=0.005; OS 19.8 vs 26.6 months (p=0.033). It was highly prognostic in the subgroup treated with gemcitabine (strong vs not-strong DFS 12.1 vs. 18.4 months; p=0.007, OS 17.9 vs 30.2 months, p=0.006), but not in the observation group (strong vs not strong DFS 6.6 vs 7.3 months p=0.767; OS 21.5 vs 18.2 months, p=0.765). Cytoplasmic SPARC expression in the adenocarcinoma cells was also associated with worse patient outcome (positive vs negative DFS 7.4 vs 12.1 months, p=0.041; OS 14.1 vs 25.6 months, p=0.011), again the effect was restricted to patients treated with gemcitabine (positive vs negative DFS 8.3 vs 15.3 months, p=0.002; OS 11.0 vs 28.8 months, p= 0.003; control group DFS 5.8 vs 7.6 months, p=0.844; OS 14.9 vs 20.8 months, p=0.519). Conclusions: Our data confirm the prognostic significance of SPARC expression and demonstrate a significant prognostic factor of SPARC in patients with pancreatic cancer after curatively intended resection. The prognostic impact was restricted to patients who received adjuvant treatment with gemcitabine. In difference to former published data this was found for peritumoral SPARC as well as for SPARC expression in tumor cells.