Cytochrome P450 1B1 expression in glial cell tumors: an immunotherapeutic target.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
CYP1B1 is frequently expressed in a variety of gliomas and could be used as a target for immunotherapy.
Barnett
Julia A
JA
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Urbauer
Diana L
DL
Murray
Graeme I
GI
Fuller
Gregory N
GN
Heimberger
Amy B
AB
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D005910:Glioma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1