title: SPARC expression in resected pancreatic cancer patients treated with gemcitabine: results from the CONKO-001 study.
abstract: BACKGROUND
  Previous investigations in pancreatic cancer suggested a prognostic role for secreted protein acidic and rich in cysteine (SPARC) expression in the peritumoral stroma but not for cytoplasmic SPARC expression. The aim of this study was to evaluate the impact of SPARC expression in pancreatic cancer patients treated with gemcitabine compared with untreated patients.
  
  
  METHODS
  CONKO-001 was a prospective randomized phase III study investigating the role of adjuvant gemcitabine when compared with observation. Tissue samples of 160 patients were available for SPARC immunohistochemistry on tissue microarrays to evaluate its impact on patient outcome.
  
  
  RESULTS
  Strong stromal SPARC expression was associated with worse disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P = 0.005, OS: P = 0.033). Its negative prognostic impact was restricted to patients treated with gemcitabine (DFS: P = 0.007, OS: P = 0.006). High cytoplasmic SPARC expression also was associated with worse patient outcome (DFS: P = 0.041, OS: P = 0.011). Again the effect was restricted to patients treated with gemcitabine (DFS: P = 0.002, OS: P = 0.003). In multivariable analysis, SPARC expression was independently predictive of patient outcome.
  
  
  CONCLUSIONS
  Our data confirm the prognostic significance of SPARC expression after curatively intended resection. The negative prognostic impact was restricted to patients who received adjuvant treatment with gemcitabine, suggesting SPARC as a predictive marker for response to gemcitabine.
authors.affiliation: Department of Medical Oncology and Haematology.
authors.forename: M
authors.initials: M
authors.lastname: Sinn
authors.forename: B V
authors.initials: BV
authors.lastname: Sinn
authors.forename: J K
authors.initials: JK
authors.lastname: Striefler
authors.forename: J L
authors.initials: JL
authors.lastname: Lindner
authors.forename: J M
authors.initials: JM
authors.lastname: Stieler
authors.forename: P
authors.initials: P
authors.lastname: Lohneis
authors.forename: S
authors.initials: S
authors.lastname: Bischoff
authors.forename: H
authors.initials: H
authors.lastname: Bläker
authors.forename: U
authors.initials: U
authors.lastname: Pelzer
authors.forename: M
authors.initials: M
authors.lastname: Bahra
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.forename: B
authors.initials: B
authors.lastname: Dörken
authors.forename: H
authors.initials: H
authors.lastname: Oettle
authors.forename: H
authors.initials: H
authors.lastname: Riess
authors.forename: C
authors.initials: C
authors.lastname: Denkert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015676:Osteonectin / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D015676:Osteonectin; C577241:SPARC protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: CONKO-001; SPARC; adjuvant therapy; gemcitabine; pancreatic cancer