title: Profiling cytochrome P450 expression in ovarian cancer: identification of prognostic markers.
abstract: OBJECTIVE
  The cytochromes P450 are a multigene family of enzymes with a central role in the oxidative metabolism of a wide range of xenobiotics, including anticancer drugs and biologically active endogenous compounds. The purpose of this study was to define the cytochrome P450 profile of ovarian cancer and identify novel therapeutic targets and establish the prognostic significance of expression of individual cytochrome P450s in this type of cancer.
  
  
  METHODS
  Immunohistochemistry for a panel of 23 cytochrome P450s and cytochrome P450 reductase was done on an ovarian cancer tissue microarray consisting of 99 primary epithelial ovarian cancers, 22 peritoneal metastasis, and 13 normal ovarian samples. The intensity of immunoreactivity in each sample was established by light microscopy.
  
  
  RESULTS
  In primary ovarian cancer, several P450s (CYP1B1, CYP2A/2B, CYP2F1, CYP2R1, CYP2U1, CYP3A5, CYP3A7, CYP3A43, CYP4Z1, CYP26A1, and CYP51) were present at a significantly higher level of intensity compared with normal ovary. P450 expression was also detected in ovarian cancer metastasis and CYP2S1 and P450 reductase both showed significantly increased expression in metastasis compared with primary ovarian cancer. The presence of low/negative CYP2A/2B (log rank = 7.06, P = 0.008) or positive CYP4Z1 (log rank = 6.19, P = 0.01) immunoreactivity in primary ovarian cancer were each associated with poor prognosis. Both CYP2A/2B and CYP4Z1 were also independent markers of prognosis.
  
  
  CONCLUSIONS
  The expression profile of individual P450s has been established in ovarian cancer. Several P450s show increased expression in ovarian cancer and this provides the basis for developing P450-based therapeutics in ovarian cancer. Expression of CYP2A/2B or CYP4Z1 in primary ovarian cancer were independent markers of prognosis.
authors.affiliation: Department of Pathology, University of Aberdee, UK.
authors.forename: Diane
authors.initials: D
authors.lastname: Downie
authors.forename: Morag C E
authors.initials: MC
authors.lastname: McFadyen
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Rooney
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Cruickshank
authors.forename: David E
authors.initials: DE
authors.lastname: Parkin
authors.forename: Iain D
authors.initials: ID
authors.lastname: Miller
authors.forename: Colin
authors.initials: C
authors.lastname: Telfer
authors.forename: William T
authors.initials: WT
authors.lastname: Melvin
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Murray
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System