Expression of Cytochrome P450 3A4 and Its Clinical Significance in Human Prostate Cancer
Expression of Cytochrome P450 3A4 and Its Clinical Significance in Human Prostate Cancer
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DOI：
10.1016/j.urology.2009.02.033
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发表时间：
2009-08-01
期刊：
影响因子：
2.1
通讯作者：
Inoue, Satoshi
中科院分区：
文献类型：
--
作者：
Fujimura, Tetsuya;Takahashi, Satoru;Inoue, Satoshi
目的评价CYP 3A 4在人前列腺癌（PCa）组织中的表达。细胞色素P450（CYP 1A 1）家族的酶是肝脏和前列腺中睾酮的关键灭活剂。我们以前曾报道，CYP 2B 6是一个生长抑制和预后因素在人类前列腺癌，然而，CYP 3A 4在前列腺癌的地位仍然不清楚。评价染色玻片的阳性染色细胞比例和染色强度。总免疫反应性评分（0-8）为比例和强度评分之和。结果CYP 3A 4免疫反应阳性表达于前列腺细胞胞浆中。CYP 3A 4免疫反应PCa评分（3.6 +/- 2.6）显著低于良性上皮（4.5 +/- 2.1; P <0.0001）。此外，CYP 3A 4免疫反应性与Gleason评分呈负相关（P < .0001）。CYP 3A 4免疫反应性降低与人前列腺癌预后不良显著相关（P = .0175）。结论我们证明了前列腺组织中CYP 3A 4的差异表达，表明CYP 3A 4表达降低可能有助于前列腺癌的发展。泌尿学74：391-397，2009年。(C)2009 Elsevier Inc.
OBJECTIVES To evaluate CYP3A4 expression in human prostrate cancer (PCa) tissues. Enzymes of the cytochrome P450 (CYP) family are key inactivators of testosterone in the liver and prostate. We previously reported that CYP2B6 is a growth-inhibitory and prognostic factor in human PCa; however, the status of CYP3A4 in PCa remains unclear.METHODS We used immunohistochemistry to analyze CYP3A4 expression in 107 human PCa specimens obtained by radical prostatectomy. Stained slides were evaluated for the proportion and staining intensity of positively stained cells. Total immunoreactivity scores (0-8) were obtained as the sum of the proportion and intensity scores. In addition, we estimated the relationship between CYP3A4 status and clinicopathologic features.RESULTS CYP3A4 immunoreactivity was identified in the cytoplasm of prostate cells. The CYP3A4 immunoreactive PCa score (3.6 +/- 2.6) was significantly lower than that of benign epithelium (4.5 +/- 2.1; P < .0001). In addition, CYP3A4 immunoreactivity correlated inversely with the Gleason score (P < .0001). Decreased CYP3A4 immunoreactivity was significantly related to a poor prognosis in human PCa (P = .0175).CONCLUSIONS We demonstrated differential CYP3A4 expression in prostatic tissues, indicating that decreased CYP3A4 expression may contribute to the development of PCa. UROLOGY 74:391-397, 2009. (C) 2009 Elsevier Inc.