title: Cytochrome p450 profile of colorectal cancer: identification of markers of prognosis.
abstract: OBJECTIVE
  The cytochromes P450 (P450) are a multigene family of enzymes with a central role in the oxidative metabolism of a wide range of xenobiotics, including anticancer drugs, carcinogens, and endogenous compounds. The purpose of this study was to define the P450 profile of colorectal cancer and establish the prognostic significance of expression of individual P450s in colorectal cancer.
  
  
  METHODS
  Immunohistochemistry for a panel of 23 P450s was done on a colorectal cancer tissue microarray consisting of 264 primary colorectal cancers, 91 lymph node metastasis, and 10 normal colorectal samples. The intensity of immunoreactivity in each sample was established by light microscopy.
  
  
  RESULTS
  The most frequently expressed form of P450 in normal colon was CYP3A4. In primary colorectal cancer, several P450s (CYP1B1, CYP2S1, CYP2U1, CYP3A5, and CYP51) were present at a significantly higher level of intensity compared with normal colon. P450 expression was also detected in lymph node metastasis and the presence of several P450s (CYP1B1, CYP2A/2B, CYP2F1, CYP4V2, and CYP39) in the lymph node metastasis strongly correlated with their presence in corresponding primary tumors. The presence of strong CYP51 (log-rank = 12.11, P = 0.0005) or strong CYP2S1 (log-rank = 6.72, P = 0.0095) immunoreactivity were associated with poor prognosis. CYP51 was also an independent marker of prognosis (P = 0.009).
  
  
  CONCLUSIONS
  The expression of individual P450s has been established in colorectal cancer. Several P450s show increased expression in colorectal cancer. High expression of CYP51 or CYP2S1 were associated with poor prognosis and CYP51 is an independent marker of prognosis.
authors.affiliation: Department of Pathology, University of Aberdeen and Auvation, Ltd., Aberdeen, United Kingdom.
authors.forename: Meera
authors.initials: M
authors.lastname: Kumarakulasingham
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Rooney
authors.forename: Sinclair R
authors.initials: SR
authors.lastname: Dundas
authors.forename: Colin
authors.initials: C
authors.lastname: Telfer
authors.forename: William T
authors.initials: WT
authors.lastname: Melvin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Curran
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Murray
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D003577:Cytochrome P-450 Enzyme System