Cytochrome P450 1B1 expression in glial cell tumors

an immunotherapeutic target

Julia A. Barnett, Diana L. Urbauer, Graeme I. Murray, Gregory N. Fuller, Amy B. Heimberger

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Purpose: Among central nervous system malignancies, cytochrome P450 1B1 (CYP1B1) expression has only been characterized in medulloblastoma. An immunotherapeutic agent targeting this antigen was shown to safely stimulate a good immune response. To evaluate the viability of further research efforts targeting this antigen, we examined the expression of CYP1B1 in glial cell malignancies.

Experimental Design: We studied the frequency and extent of CYP1B1 expression by immunohistochemical analysis in 269 glial tumors (including all major pathologic types) on a tissue microarray. Results were categorized by percentage of cells stained and intensity of cytoplasmic staining within cells. Correlation of CYP1B1 expression with patient prognosis was evaluated by univariate and multivariate analyses.

Results: Overall, increased CYP1B1 expression in glial tumors was associated with decreased patient survival time (P < 0.0014 for both percentage and intensity of staining). A significant difference existed in percentage and intensity of staining between astrocytic and oligodendroglial tumors (P = 0.0002 and 0.0003, respectively), between grades of tumors (P < 0.0001 and 0.0079), and between pathologic types of tumors (P < 0.0001 and 0.0339). Positive CYP1B1 staining was seen in 81% of glioblastomas, 84% of anaplastic astrocytomas, 61% of oligodendrogliomas, and 67% of anaplastic oligodendrogliomas. Paradoxically, within specific tumor pathologies, there was a trend toward increased survival as CYP1B1 expression increased. However, in the multivariate analysis, this trend disappeared, and CYP1B1 expression seemed prognostically neutral.

Conclusion: CYP1B1 is frequently expressed in a variety of gliomas and could be used as a target for immunotherapy.

Original languageEnglish
Pages (from-to)3559-3567
Number of pages9
JournalClinical Cancer Research
Volume13
Issue number12
DOIs
Publication statusPublished - 15 Jun 2007

Keywords

  • growth-factor receptor
  • activated cancer-chemotherapy
  • cytotoxic T-cells
  • glioblastoma-multiforme
  • prognostic markers
  • human gliomas
  • brain-tumors
  • CYP1B1
  • oligodendrogliomas
  • vaccination

Cite this

Cytochrome P450 1B1 expression in glial cell tumors : an immunotherapeutic target. / Barnett, Julia A.; Urbauer, Diana L.; Murray, Graeme I.; Fuller, Gregory N.; Heimberger, Amy B.

In: Clinical Cancer Research, Vol. 13, No. 12, 15.06.2007, p. 3559-3567.

Research output: Contribution to journalArticle

Barnett, Julia A. ; Urbauer, Diana L. ; Murray, Graeme I. ; Fuller, Gregory N. ; Heimberger, Amy B. / Cytochrome P450 1B1 expression in glial cell tumors : an immunotherapeutic target. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 12. pp. 3559-3567.
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abstract = "Purpose: Among central nervous system malignancies, cytochrome P450 1B1 (CYP1B1) expression has only been characterized in medulloblastoma. An immunotherapeutic agent targeting this antigen was shown to safely stimulate a good immune response. To evaluate the viability of further research efforts targeting this antigen, we examined the expression of CYP1B1 in glial cell malignancies. Experimental Design: We studied the frequency and extent of CYP1B1 expression by immunohistochemical analysis in 269 glial tumors (including all major pathologic types) on a tissue microarray. Results were categorized by percentage of cells stained and intensity of cytoplasmic staining within cells. Correlation of CYP1B1 expression with patient prognosis was evaluated by univariate and multivariate analyses. Results: Overall, increased CYP1B1 expression in glial tumors was associated with decreased patient survival time (P < 0.0014 for both percentage and intensity of staining). A significant difference existed in percentage and intensity of staining between astrocytic and oligodendroglial tumors (P = 0.0002 and 0.0003, respectively), between grades of tumors (P < 0.0001 and 0.0079), and between pathologic types of tumors (P < 0.0001 and 0.0339). Positive CYP1B1 staining was seen in 81{\%} of glioblastomas, 84{\%} of anaplastic astrocytomas, 61{\%} of oligodendrogliomas, and 67{\%} of anaplastic oligodendrogliomas. Paradoxically, within specific tumor pathologies, there was a trend toward increased survival as CYP1B1 expression increased. However, in the multivariate analysis, this trend disappeared, and CYP1B1 expression seemed prognostically neutral. Conclusion: CYP1B1 is frequently expressed in a variety of gliomas and could be used as a target for immunotherapy.",
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T2 - an immunotherapeutic target

AU - Barnett, Julia A.

AU - Urbauer, Diana L.

AU - Murray, Graeme I.

AU - Fuller, Gregory N.

AU - Heimberger, Amy B.

PY - 2007/6/15

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N2 - Purpose: Among central nervous system malignancies, cytochrome P450 1B1 (CYP1B1) expression has only been characterized in medulloblastoma. An immunotherapeutic agent targeting this antigen was shown to safely stimulate a good immune response. To evaluate the viability of further research efforts targeting this antigen, we examined the expression of CYP1B1 in glial cell malignancies. Experimental Design: We studied the frequency and extent of CYP1B1 expression by immunohistochemical analysis in 269 glial tumors (including all major pathologic types) on a tissue microarray. Results were categorized by percentage of cells stained and intensity of cytoplasmic staining within cells. Correlation of CYP1B1 expression with patient prognosis was evaluated by univariate and multivariate analyses. Results: Overall, increased CYP1B1 expression in glial tumors was associated with decreased patient survival time (P < 0.0014 for both percentage and intensity of staining). A significant difference existed in percentage and intensity of staining between astrocytic and oligodendroglial tumors (P = 0.0002 and 0.0003, respectively), between grades of tumors (P < 0.0001 and 0.0079), and between pathologic types of tumors (P < 0.0001 and 0.0339). Positive CYP1B1 staining was seen in 81% of glioblastomas, 84% of anaplastic astrocytomas, 61% of oligodendrogliomas, and 67% of anaplastic oligodendrogliomas. Paradoxically, within specific tumor pathologies, there was a trend toward increased survival as CYP1B1 expression increased. However, in the multivariate analysis, this trend disappeared, and CYP1B1 expression seemed prognostically neutral. Conclusion: CYP1B1 is frequently expressed in a variety of gliomas and could be used as a target for immunotherapy.

AB - Purpose: Among central nervous system malignancies, cytochrome P450 1B1 (CYP1B1) expression has only been characterized in medulloblastoma. An immunotherapeutic agent targeting this antigen was shown to safely stimulate a good immune response. To evaluate the viability of further research efforts targeting this antigen, we examined the expression of CYP1B1 in glial cell malignancies. Experimental Design: We studied the frequency and extent of CYP1B1 expression by immunohistochemical analysis in 269 glial tumors (including all major pathologic types) on a tissue microarray. Results were categorized by percentage of cells stained and intensity of cytoplasmic staining within cells. Correlation of CYP1B1 expression with patient prognosis was evaluated by univariate and multivariate analyses. Results: Overall, increased CYP1B1 expression in glial tumors was associated with decreased patient survival time (P < 0.0014 for both percentage and intensity of staining). A significant difference existed in percentage and intensity of staining between astrocytic and oligodendroglial tumors (P = 0.0002 and 0.0003, respectively), between grades of tumors (P < 0.0001 and 0.0079), and between pathologic types of tumors (P < 0.0001 and 0.0339). Positive CYP1B1 staining was seen in 81% of glioblastomas, 84% of anaplastic astrocytomas, 61% of oligodendrogliomas, and 67% of anaplastic oligodendrogliomas. Paradoxically, within specific tumor pathologies, there was a trend toward increased survival as CYP1B1 expression increased. However, in the multivariate analysis, this trend disappeared, and CYP1B1 expression seemed prognostically neutral. Conclusion: CYP1B1 is frequently expressed in a variety of gliomas and could be used as a target for immunotherapy.

KW - growth-factor receptor

KW - activated cancer-chemotherapy

KW - cytotoxic T-cells

KW - glioblastoma-multiforme

KW - prognostic markers

KW - human gliomas

KW - brain-tumors

KW - CYP1B1

KW - oligodendrogliomas

KW - vaccination

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DO - 10.1158/1078-0432.CCR-06-2430

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SP - 3559

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JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

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ER -