Barnett Julia A, Urbauer Diana L, Murray Graeme I, Fuller Gregory N, Heimberger Amy B
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2007 Jun 15;13(12):3559-67. doi: 10.1158/1078-0432.CCR-06-2430.
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.
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.
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.
CYP1B1 is frequently expressed in a variety of gliomas and could be used as a target for immunotherapy.
在中枢神经系统恶性肿瘤中，细胞色素P450 1B1（CYP1B1）的表达仅在髓母细胞瘤中得到表征。一种靶向该抗原的免疫治疗药物被证明能安全地刺激良好的免疫反应。为了评估针对该抗原进一步研究的可行性，我们检测了CYP1B1在胶质细胞恶性肿瘤中的表达。
我们通过免疫组织化学分析，在组织芯片上研究了269例胶质肿瘤（包括所有主要病理类型）中CYP1B1表达的频率和程度。结果根据染色细胞的百分比和细胞内细胞质染色强度进行分类。通过单变量和多变量分析评估CYP1B1表达与患者预后的相关性。
总体而言，胶质肿瘤中CYP1B1表达增加与患者生存时间缩短相关（染色百分比和强度的P值均<0.0014）。星形细胞瘤和少突胶质细胞瘤之间的染色百分比和强度存在显著差异（分别为P = 0.0002和0.0003），肿瘤分级之间存在显著差异（P < 0.0001和0.0079），肿瘤病理类型之间存在显著差异（P < 0.0001和0.0339）。在81%的胶质母细胞瘤、84%的间变性星形细胞瘤、61%的少突胶质细胞瘤和67%的间变性少突胶质细胞瘤中可见CYP1B1阳性染色。矛盾的是，在特定的肿瘤病理类型中，随着CYP1B1表达增加，生存有增加的趋势。然而，在多变量分析中，这种趋势消失了，CYP1B1表达在预后方面似乎呈中性。
CYP1B1在多种胶质瘤中频繁表达，可作为免疫治疗的靶点。
