title: Nuclear maspin expression as a predictive marker for fluorouracil treatment response in colon cancer.
abstract: BACKGROUND
  Maspin is a member of the serpin family of protease inhibitors whose function in colorectal cancer is not fully understood. The objective of this study was to determine whether level of maspin expression could have prognostic or predictive value in colorectal cancer.
  
  
  METHODS
  Maspin expression was assessed using immunohistochemistry on tissue microarrays obtained from 380 patients with stage II and III colorectal cancer randomized to adjuvant chemotherapy with fluorouracil and levamisole (5-FU/Lev) or to surgery only (control), with scores (0-300) based on presence (0-100) and intensity (0-3) of maspin expression. Associations with disease-free survival (DFS), cancer-specific survival (CSS) and prognostic factors were determined.
  
  
  RESULTS
  Maspin expression was predominantly nuclear and present in tumor tissue in 99% of the cases. No associations with clinicopathological factors were identified. In colon cancer patients receiving adjuvant chemotherapy, maspin expression level was significantly associated with CSS [HR 1.43 per 50 points increase in maspin score (p = 0.021)] in multivariate analyses, and a significant interaction between treatment status and maspin expression (p = 0.045) was found. Kaplan-Meier plots from colon cancer patients showed a significant treatment benefit in patients with low maspin expression, but not for individuals with medium/high expression. Level of maspin expression was not significantly related to clinical outcome in rectal cancer or in any of the control groups.
  
  
  CONCLUSIONS
  In patients with colon cancer a low nuclear maspin expression was an independent predictor of benefit from adjuvant chemotherapy with 5-FU/Lev. A prognostic value of maspin expression was not found in this material.
authors.affiliation: Department of Oncology, Haukeland University Hospital , Bergen , Norway.
authors.forename: Kjersti Elvestad
authors.initials: KE
authors.lastname: Hestetun
authors.forename: Marianne
authors.initials: M
authors.lastname: Brydøy
authors.forename: Mette Pernille
authors.initials: MP
authors.lastname: Myklebust
authors.forename: Olav
authors.initials: O
authors.lastname: Dahl
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000368:Aged; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007978:Levamisole / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D012189:Retrospective Studies; D015843:Serpins / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C085344:SERPIN-B5; D015843:Serpins; D007978:Levamisole; D005472:Fluorouracil