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分析乳腺癌中细胞色素 P450 的表达情况。

Profiling the expression of cytochrome P450 in breast cancer.

机构信息

Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.

出版信息

Histopathology. 2010 Aug;57(2):202-11. doi: 10.1111/j.1365-2559.2010.03606.x.

DOI:10.1111/j.1365-2559.2010.03606.x
PMID:20716162
Abstract

AIMS

The cytochrome P450s (P450) are key oxidative enzymes that metabolize many carcinogens and anticancer drugs. Thus, these enzymes influence tumour development, tumour response to therapy and are putative tumour biomarkers. The aim was to define the P450 expression profile in breast cancer and establish the significance of P450 expression in this tumour type.

METHODS AND RESULTS

A tissue microarray containing 170 breast cancers of no special type was immunostained for a panel of 21 P450s. The highest percentage of strong immunopositivity in breast cancers was seen for CYP4X1 (50.8%), CYP2S1 (37.5%) and CYP2U1 (32.2%), while CYP2J (98.6%) and CYP3A43 (70.7%) were the P450s that most frequently displayed no immunoreactivity. CYP4V2 (P = 0.01), CYP4X1 (P = 0.01) and CYP4Z1 (P = 0.01) showed correlations with tumour grade. CYP1B1 (P = 0.001), CYP3A5 (P = 0.001) and CYP51 (P = 0.005) showed the most significant correlations with oestrogen receptor status. Correlations with survival were identified for CYP2S1 (P = 0.03), CYP3A4 (P = 0.025), CYP4V2 (P = 0.026) and CYP26A1 (P = 0.03), although none of these P450s was an independent marker of prognosis.

CONCLUSIONS

This study has defined the expression profile of cytochrome P450s in breast cancer and may offer their potential application as biomarkers to aid decisions regarding optimal adjuvant hormonal therapy.

摘要

目的

细胞色素 P450 酶(P450)是代谢许多致癌物质和抗癌药物的关键氧化酶。因此,这些酶影响肿瘤的发展、肿瘤对治疗的反应,并且是潜在的肿瘤生物标志物。本研究旨在确定乳腺癌中 P450 的表达谱,并确定 P450 在这种肿瘤类型中的表达意义。

方法和结果

使用包含 170 例非特殊类型乳腺癌的组织微阵列对 21 种 P450 进行免疫染色。在乳腺癌中,CYP4X1(50.8%)、CYP2S1(37.5%)和 CYP2U1(32.2%)的强免疫阳性率最高,而 CYP2J(98.6%)和 CYP3A43(70.7%)则是免疫反应性最低的 P450。CYP4V2(P=0.01)、CYP4X1(P=0.01)和 CYP4Z1(P=0.01)与肿瘤分级相关。CYP1B1(P=0.001)、CYP3A5(P=0.001)和 CYP51(P=0.005)与雌激素受体状态的相关性最显著。CYP2S1(P=0.03)、CYP3A4(P=0.025)、CYP4V2(P=0.026)和 CYP26A1(P=0.03)的生存相关性被确定,但这些 P450 都不是独立的预后标志物。

结论

本研究定义了乳腺癌中细胞色素 P450 的表达谱,可能为辅助决策最佳辅助激素治疗提供潜在的应用价值。

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