| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Imaging, Diagnosis, Prognosis |
Authors' Affiliations: 1 Department of Pathology, University of Aberdeen and 2 Auvation, Ltd., Aberdeen, United Kingdom
Requests for reprints: Graeme I. Murray, Department of Pathology, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, United Kingdom. Phone: 44-1224-553794; Fax: 44-1224-663002; E-mail: g.i.murray{at}abdn.ac.uk.
Purpose: 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.
Experimental Design: 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.
Key Words: Immunohistochemistry • prognostic marker • survival • tissue microarray
This article has been cited by other articles:
|
|
 |
|
  J.-M. SU, P. LIN, C.-K. WANG, and H. CHANG Overexpression of Cytochrome P450 1B1 in Advanced Non-small Cell Lung Cancer: A Potential Therapeutic Target Anticancer Res, February 1, 2009; 29(2): 509 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Halberg, M. C. Larsen, T. L. Elmergreen, A. Y. Ko, A. A. Irving, L. Clipson, and C. R. Jefcoate Cyp1b1 Exerts Opposing Effects on Intestinal Tumorigenesis via Exogenous and Endogenous Substrates Cancer Res., September 15, 2008; 68(18): 7394 - 7402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Barnett, D. L. Urbauer, G. I. Murray, G. N. Fuller, and A. B. Heimberger Cytochrome P450 1B1 Expression in Glial Cell Tumors: An Immunotherapeutic Target Clin. Cancer Res., June 15, 2007; 13(12): 3559 - 3567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Rivera, F. Wang, S. T. Saarikoski, R. T. Taylor, B. Chapman, R. Zhang, and O. Hankinson A Novel Promoter Element Containing Multiple Overlapping Xenobiotic and Hypoxia Response Elements Mediates Induction of Cytochrome P4502S1 by Both Dioxin and Hypoxia J. Biol. Chem., April 13, 2007; 282(15): 10881 - 10893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ekins, D. C. Mankowski, D. J. Hoover, M. P. Lawton, J. L. Treadway, and H. J. Harwood Jr. Three-Dimensional Quantitative Structure-Activity Relationship Analysis of Human CYP51 Inhibitors Drug Metab. Dispos., March 1, 2007; 35(3): 493 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Al-Mulla, S. Hagan, A. I. Behbehani, M. S. Bitar, S. S. George, J. J. Going, J. J. C. Garcia, L. Scott, N. Fyfe, G. I. Murray, et al. Raf Kinase Inhibitor Protein Expression in a Survival Analysis of Colorectal Cancer Patients J. Clin. Oncol., December 20, 2006; 24(36): 5672 - 5679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-R. Zhu, P. E. Thomas, G. Lu, K. R. Reuhl, G.-Y. Yang, L.-D. Wang, S.-L. Wang, C. S. Yang, X.-Y. He, and J.-Y. Hong CYP2A13 in Human Respiratory Tissues and Lung Cancers: An Immunohistochemical Study with A New Peptide-Specific Antibody Drug Metab. Dispos., October 1, 2006; 34(10): 1672 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Downie, M. C.E. McFadyen, P. H. Rooney, M. E. Cruickshank, D. E. Parkin, I. D. Miller, C. Telfer, W. T. Melvin, and G. I. Murray Profiling Cytochrome P450 Expression in Ovarian Cancer: Identification of Prognostic Markers Clin. Cancer Res., October 15, 2005; 11(20): 7369 - 7375. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
