Expression of S100A2 calcium-binding protein predicts response to pancreatectomy for pancreatic cancer

Andrew V. Biankin, James G. Kench, Emily K. Colvin, Davendra Segara, Christopher J. Scarlett, Nam Q. Nguyen, David K. Chang, Adrienne L. Morey, C.-Soon Lee, Mark Pinese, Samuel C. L. Kuo, Johana M. Susanto, Peter H. Cosman, Geoffrey J. Lindeman, Jane E. Visvader, Tuan V. Nguyen, Neil D. Merrett, Janindra Warusavitarne, Elizabeth A. Musgrove, Susan M. HenshallRobert L. Sutherland

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background & Aims Current methods of preoperative staging and predicting outcome following pancreatectomy for pancreatic cancer (PC) are inadequate. We evaluated the utility of multiple biomarkers from distinct biologic pathways as potential predictive markers of response to pancreatectomy and patient survival. Methods We assessed the relationship of candidate biomarkers known, or suspected, to be aberrantly expressed in PC, with disease-specific survival and response to therapy in a cohort of 601 patients. Results Of the 17 candidate biomarkers examined, only elevated expression of S100A2 was an independent predictor of survival in both the training (n = 162) and validation sets (n = 439; hazard ratio [HR], 2.19; 95% confidence interval [CI]: 1.48–3.25; P < .0001) when assessed in a multivariate model with clinical variables. Patients with high S100A2 expressing tumors had no survival benefit with pancreatectomy compared with those with locally advanced disease, whereas those without high S100A2 expression had a survival advantage of 10.6 months (19.4 vs 8.8 months, respectively) and a HR of 3.23 (95% CI: 2.39–4.33; P < .0001). Of significance, patients with S100A2-negative tumors had a significant survival benefit from pancreatectomy even in the presence of involved surgical margins (median, 15.7 months; P = .0007) or lymph node metastases (median, 17.4 months; P = .0002). Conclusions S100A2 expression is a good predictor of response to pancreatectomy for PC and suggests that high S100A2 expression may be a marker of a metastatic phenotype. Prospective measurement of S100A2 expression in diagnostic biopsy samples has potential clinical utility as a predictive marker of response to pancreatectomy and other therapies that target locoregional disease.
    Original languageEnglish
    Pages (from-to)558-56800000000000
    Number of pages22
    JournalGastroenterology
    Volume137
    Issue number2
    DOIs
    Publication statusPublished - 2009

    Keywords

    • pancreatectomy
    • pancreatic cancer

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