Profiling cytochrome P450 expression in ovarian cancer

Identification of prognostic markers

D. Downie, M. C. E. McFadyen, P. H. Rooney, M. E. Cruickshank, David Parkin, Iain D Miller, C. Telfer, W. T. Melvin, Graeme Ian Murray

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Purpose: 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.

Experimental Design: Immunohistochemistry for a panel of 23 cylochrome 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.

Original languageEnglish
Pages (from-to)7369-7375
Number of pages6
JournalClinical Cancer Research
Volume11
DOIs
Publication statusPublished - 2005

Keywords

  • xenobiotic-metabolizing enzymes
  • breast-cancer
  • tumor
  • P450CYP1B1
  • localization
  • CYP1B1
  • P450
  • chemotherapy
  • activation
  • toxicity

Cite this

Downie, D., McFadyen, M. C. E., Rooney, P. H., Cruickshank, M. E., Parkin, D., Miller, I. D., ... Murray, G. I. (2005). Profiling cytochrome P450 expression in ovarian cancer: Identification of prognostic markers. Clinical Cancer Research, 11, 7369-7375. https://doi.org/10.1158/1078-0432.CCR-05-0466

Profiling cytochrome P450 expression in ovarian cancer : Identification of prognostic markers. / Downie, D.; McFadyen, M. C. E.; Rooney, P. H.; Cruickshank, M. E.; Parkin, David; Miller, Iain D; Telfer, C.; Melvin, W. T.; Murray, Graeme Ian.

In: Clinical Cancer Research, Vol. 11, 2005, p. 7369-7375.

Research output: Contribution to journalArticle

Downie, D, McFadyen, MCE, Rooney, PH, Cruickshank, ME, Parkin, D, Miller, ID, Telfer, C, Melvin, WT & Murray, GI 2005, 'Profiling cytochrome P450 expression in ovarian cancer: Identification of prognostic markers', Clinical Cancer Research, vol. 11, pp. 7369-7375. https://doi.org/10.1158/1078-0432.CCR-05-0466
Downie, D. ; McFadyen, M. C. E. ; Rooney, P. H. ; Cruickshank, M. E. ; Parkin, David ; Miller, Iain D ; Telfer, C. ; Melvin, W. T. ; Murray, Graeme Ian. / Profiling cytochrome P450 expression in ovarian cancer : Identification of prognostic markers. In: Clinical Cancer Research. 2005 ; Vol. 11. pp. 7369-7375.
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abstract = "Purpose: 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.Experimental Design: Immunohistochemistry for a panel of 23 cylochrome 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.",
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author = "D. Downie and McFadyen, {M. C. E.} and Rooney, {P. H.} and Cruickshank, {M. E.} and David Parkin and Miller, {Iain D} and C. Telfer and Melvin, {W. T.} and Murray, {Graeme Ian}",
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TY - JOUR

T1 - Profiling cytochrome P450 expression in ovarian cancer

T2 - Identification of prognostic markers

AU - Downie, D.

AU - McFadyen, M. C. E.

AU - Rooney, P. H.

AU - Cruickshank, M. E.

AU - Parkin, David

AU - Miller, Iain D

AU - Telfer, C.

AU - Melvin, W. T.

AU - Murray, Graeme Ian

PY - 2005

Y1 - 2005

N2 - Purpose: 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.Experimental Design: Immunohistochemistry for a panel of 23 cylochrome 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.

AB - Purpose: 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.Experimental Design: Immunohistochemistry for a panel of 23 cylochrome 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.

KW - xenobiotic-metabolizing enzymes

KW - breast-cancer

KW - tumor

KW - P450CYP1B1

KW - localization

KW - CYP1B1

KW - P450

KW - chemotherapy

KW - activation

KW - toxicity

U2 - 10.1158/1078-0432.CCR-05-0466

DO - 10.1158/1078-0432.CCR-05-0466

M3 - Article

VL - 11

SP - 7369

EP - 7375

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

ER -