title: The expression of CYP2W1: a prognostic marker in colon cancer.
abstract: OBJECTIVE
  The enzyme Cytochrome P450 2W1 (CYP2W1) is found in fetal colon tissue and is also detected in colorectal cancer but not in non-transformed tissue. In a pilot study, we reported that the immunohistochemically-detected expression of CYP2W1 might be of prognostic value since high expression of CYP2W1 was indicative of a worse prognosis. The aim of this study was to validate the pilot study's results using a larger, independent group of patients with colon cancer.
  
  
  METHODS
  Immunohistochemical detection of CYP2W1 in 235 malignant colon tumors of stage II and III, was carried out using a polyclonal antibody. Grading of staining was carried out by two independent readers. The highest grade that involved more than 5% of the tumor area on each slide was used for the classification of CYP2W1 expression.
  
  
  RESULTS
  CYP2W1 was expressed at high levels in 30% of the tumors. In the entire colon cancer group it was an independent prognostic factor in multivariate analysis (p=0.04), where high expression (grade 3) correlated with worse outcome. CYP2W1 expression was an independent prognostic factor in the subgroup of patients with colon cancer stage III (p=0.003), but not for those with stage II. In 107 cases, two slices from different areas of the same tumor were available, and no significant difference in CYP2W1 expression between the slices was observed (r=0.53, p<0.001).
  
  
  CONCLUSIONS
  The results of the current study were in agreement with those of the previous pilot study and show that higher expression of CYP2W1 seems to be of prognostic value in colon cancer. Furthermore, we found equal expression in slices from two different areas of the same tumor. Since the CYP2W1 enzyme has been shown to catalytically activate compounds to cytotoxic products, the enzyme might be used as a novel drug target for the treatment of colon cancer.
authors.affiliation: Department of 1Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. kristina.stenstedt@ki.se
authors.forename: Kristina
authors.initials: K
authors.lastname: Stenstedt
authors.forename: Maria
authors.initials: M
authors.lastname: Hallstrom
authors.forename: Inger
authors.initials: I
authors.lastname: Johansson
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Peter
authors.initials: P
authors.lastname: Ragnhammar
authors.forename: David
authors.initials: D
authors.lastname: Edler
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D000072467:Cytochrome P450 Family 2; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D003577:Cytochrome P-450 Enzyme System; C509336:CYP2W1 protein, human; D000072467:Cytochrome P450 Family 2