title: The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy.
abstract: BACKGROUND
  Pancreatic ductal adenocarcinoma (PDA) is comprised of a prominent desmoplastic stromal compartment and only 10-40% of the tumour consists of PDA cells. However, how stromal components should be assessed and how the characteristics of the stromal compartment determine clinical outcomes in PDA patients remain unknown.
  
  
  METHODS
  A cohort of 66 consecutive patients who underwent pancreaticoduodenectomy and were primarily followed at Johns Hopkins Hospital between 1998 and 2004, and treated with adjuvant therapy, were included in a retrospective analysis. Resected PDA blocks with good tissue preservation were available for all patients. A new, computer-aided, quantitative method was developed to assess the density and activity of stroma in PDAs and the associations of these characteristics with clinical outcomes.
  
  
  RESULTS
  High stromal density in resected PDA was found to be significantly associated with longer disease-free [adjusted hazard ratio (aHR) 0.39; P = 0.001] and overall (aHR 0.44; P = 0.004) survival after adjusting for the use of pancreatic cancer vaccine therapy, as well as gender and resection margin positivity. Stromal activity, representing activated pancreatic stellate cells in PDAs, was not significantly associated with the prognosis of resected PDAs.
  
  
  CONCLUSIONS
  These results illustrate the complexity of the role of stroma in PDAs. Further exploration of the prognostic ability of the characteristics of stroma is warranted.
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Bever
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Sugar
authors.forename: Elaine
authors.initials: E
authors.lastname: Bigelow
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Daniel
authors.initials: D
authors.lastname: Laheru
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Jaffee
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.forename: Ana
authors.initials: A
authors.lastname: De Jesus-Acosta
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015142:Baltimore; D014408:Biomarkers, Tumor / Q000032:analysis; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D003094:Collagen / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007633:Keratins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D016577:Pancreaticoduodenectomy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; D007633:Keratins; D003094:Collagen