title: α-Smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study.
abstract: BACKGROUND
  Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin (α-SMA) expression and stromal density in the peritumoural stroma. The aim of this study was to further validate the impact of α-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients.
  
  
  METHODS
  CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation. Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of α-SMA expression and stromal density impact on patient outcome.
  
  
  RESULTS
  High α-SMA expression in tumour stroma was associated with worse patient outcome (DFS: P=0.05, OS: P=0.047). A dense stroma reaction was associated with improved disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P=0.001, OS: P=0.001). This positive prognostic impact was restricted to patients with no adjuvant treatment (DFS: P<0.001, OS: P<0.001). In multivariable analysis, α-SMA and stromal density expression were independently predictive factors for survival.
  
  
  CONCLUSIONS
  Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection. In contrast to former investigations, we found a positive prognostic impact for a dense stroma. This significant influence was restricted to patients who received no adjuvant therapy.
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sinn
authors.affiliation: Charité-Universitätsmedizin Berlin, Institute of Pathology, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Denkert
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: J K
authors.initials: JK
authors.lastname: Striefler
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Pelzer
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: J M
authors.initials: JM
authors.lastname: Stieler
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of General, Visceral and Transplantation Surgery, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bahra
authors.affiliation: Charité-Universitätsmedizin Berlin, Institute of Pathology, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Lohneis
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Dörken
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Oettle
authors.affiliation: Charité-Universitätsmedizin Berlin, Department of Medical Oncology and Haematology, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Riess
authors.affiliation: Charité-Universitätsmedizin Berlin, Institute of Pathology, Chariteplatz 1, 10117 Berlin, Germany.
authors.forename: B V
authors.initials: BV
authors.lastname: Sinn
mesh_terms: D000199:Actins / Q000378:metabolism*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment; D000093542:Gemcitabine
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D000093542:Gemcitabine