Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)319-325
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number3
DOIs
StatePublished - Jan 20 2007

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Cysteine
Adenocarcinoma
Fibroblasts
Proteins
Pancreatic Neoplasms
Neoplasms
Kaplan-Meier Estimate
Baltimore
Pancreaticoduodenectomy
Survival
Epigenomics
Cell Communication
Cell Movement
Lymph Nodes
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. / Infante, Jeffrey R.; Matsubayashi, Hiroyuki; Sato, Norihiro; Tonascia, James A; Klein, Alison; Riall, Taylor A.; Yeo, Charles; Iacobuzio-Donahue, Christine; Goggins, Michael S.

In: Journal of Clinical Oncology, Vol. 25, No. 3, 20.01.2007, p. 319-325.

Research output: Contribution to journalArticle

Infante, Jeffrey R. ; Matsubayashi, Hiroyuki ; Sato, Norihiro ; Tonascia, James A ; Klein, Alison ; Riall, Taylor A. ; Yeo, Charles ; Iacobuzio-Donahue, Christine ; Goggins, Michael S. / Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 3. pp. 319-325.
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abstract = "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.",
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T1 - Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma

AU - Infante, Jeffrey R.

AU - Matsubayashi, Hiroyuki

AU - Sato, Norihiro

AU - Tonascia, James A

AU - Klein, Alison

AU - Riall, Taylor A.

AU - Yeo, Charles

AU - Iacobuzio-Donahue, Christine

AU - Goggins, Michael S

PY - 2007/1/20

Y1 - 2007/1/20

N2 - 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.

AB - 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.

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