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Peritumoral Fibroblast SPARC Expression and Patient Outcome With Resectable Pancreatic Adenocarcinoma

Jeffrey R. Infante, Hiroyuki Matsubayashi, Norihiro Sato, James Tonascia, Alison P. Klein, Taylor A. Riall, Charles Yeo, Christine Iacobuzio-Donahue, Michael Goggins

From the Departments of Pathology, Oncology, and Medicine, Surgery and Epidemiology and Biostatistics, and The Sol Goldman Pancreatic Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD

Address reprint requests to Michael Goggins, MD, Departments of Pathology, Medicine, and Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, 1550 Orleans St, Baltimore, MD 21205; e-mail: mgoggins{at}jhmi.edu

PURPOSE: SPARC (secreted protein acidic and rich in cysteine) is a protein involved in cell matrix interactions, wound repair, and cell migration, and has been reported to inhibit cancer growth. SPARC undergoes epigenetic silencing in many pancreatic cancers, but stromal fibroblasts adjacent to infiltrating pancreatic adenocarcinomas frequently express SPARC. We evaluated the prognostic significance of tumor and peritumoral SPARC expression in patients with pancreatic adenocarcinoma.

PATIENTS AND METHODS: The expression patterns of SPARC were characterized by immunohistochemistry in 299 primary pancreatic ductal adenocarcinoma resection specimens from patients who underwent pancreaticoduodenectomy at Johns Hopkins Hospital (Baltimore, MD) between 1998 and 2003. Kaplan-Meier analysis and Cox proportional hazards regression modeling were used to assess the mortality risk associated with the presence or absence of tumor SPARC and peritumoral SPARC status.

RESULTS: By Kaplan-Meier analysis, patients whose pancreatic cancer stromal fibroblasts expressed SPARC (median survival, 15 months) had a significantly worse prognosis than patients whose tumor stroma did not express SPARC (median survival, 30 months; log-rank P < .001). In contrast, the expression of SPARC in pancreatic cancer cells was not associated with prognosis (log-rank P = .13). Controlling for other prognostic factors (tumor size, positive lymph nodes, margin status, tumor grade, and age), the relative hazard for patients whose stroma expressed SPARC compared with those whose stroma did not was 1.89 (95% CI, 1.31 to 2.74); the expression of SPARC in pancreatic cancer cells remained unrelated to prognosis (relative hazard, 1.02; 95% CI, 0.73 to 1.42).

CONCLUSION: The expression of SPARC by peritumoral fibroblasts portends a poorer prognosis for patients with pancreatic cancer.

Supported by Grants No. CA90709 and CA62924 from the National Cancer Institute, and the Michael Rolfe Foundation.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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