title: Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  The expression of SPARC by peritumoral fibroblasts portends a poorer prognosis for patients with pancreatic cancer.
authors.affiliation: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Infante
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsubayashi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: James
authors.initials: J
authors.lastname: Tonascia
authors.forename: Alison P
authors.initials: AP
authors.lastname: Klein
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Riall
authors.forename: Charles
authors.initials: C
authors.lastname: Yeo
authors.forename: Christine
authors.initials: C
authors.lastname: Iacobuzio-Donahue
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000601:surgery; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015676:Osteonectin / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015676:Osteonectin