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Application of cytochrome P-450 of human fetal liber(P-450HFLa) as a tumor marker

人胎儿细胞色素P-450(P-450HFLa)作为肿瘤标志物的应用

基本信息

批准号：
03670768
负责人：
OKAJIMA Yuko
金额：
$ 1.22万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

Cytochrome P-450 of human fetal livers(P-450HFLa) was demonstrated by the immunoperoxidase techniquw in tissue samples as follows ; human fetal organs, and cynomolgus placenta, and gynecologic organs which were obtained from 40 patients gynecologic malignancies and 32 patients with benign diseases.P-450HFLa was clearly localized in the cytoplasm and membranes of hepatocytes, and the fact was cofirmed immunoelectron micro-scopically. In addition. semiquantitative assay of staining intensity demonstrated that this tended to decrease with adbancing age.These findings suggest that hepatic P-450HFLa synthesis is inversely proportional to age, and that this enzyme is one of the differentia-tion antigens.P-450HFLa was also detected immunohistochemically in other fetal organs. The present study thus confirms that P-450HFLa is not specific to the liber and is ubiquitous even in the fetus. Marked positive stanining for P-450HFLa was demonstrated in villous syncytiotropho-blasts. In contrast, nop … More ositive staining was found in the cynomolgus monkey placenta, unlike the case for many other plactal antigens. These findings lead to the tentative conclusion that P-450HFLa is a fetoplacental enzyme peculiar to humans.P-450HFLa was denonstrated to occur very frequently in gynecologic malignancies. the mean positivity rate for all gynecologic malignancies was 85%, while the rate was gelow 25% for benign gyne-cologic diseases, indicating that P-450HFLa is the one of the onco-teto-placental enzymes.We established an enzyme immunoassay for P-450HFLa by utilizing the avidin-biotin-peroxidase reaction, and determined that the normal range was >3.0 units/ml. In weeks 4-42 of pregnancy, the P-450HFLa level ranged from 0 to 38 units/ml. It rose during the first tri-mester, fell during the second trimester, and the increased again during the third trimester. After delivery, the serum P-450HFLa con-centration immediately returned to the nonpregnant level. The posi-tivity rate was 0% in patients with benign ovarian neoplasms, 71% in thosw with endometriosis, and 10% in those with uterine myoma. The positivity rate was 100% in patients with both ovarian and endometrial carcinoma. In patients with cervical carcinoma, the positivity rate was 78%, but the absolute values were not markedly raised in comparison with those in healthy nonpregnant woman. The present study suggests that this enzyme could be used as a new screening marker for gynecologic malignancy in patients without endometriosis, but would be inadequate as a monitoring marker because of the amall difference between normal and pathological level. Less

通过免疫过氧化物酶技术在组织样本中证实了人胎肝脏的细胞色素 P-450 (P-450HFLa) 如下；取自40例妇科恶性肿瘤和32例良性疾病患者的人类胎儿器官、食蟹猴胎盘和妇科器官。P-450HFLa明确定位于肝细胞的细胞质和细胞膜中，这一事实得到了免疫电镜证实。此外。染色强度的半定量分析表明，随着年龄的增长，这种染色强度往往会降低。这些结果表明，肝脏 P-450HFLa 的合成与年龄成反比，并且该酶是分化抗原之一。在其他胎儿器官中也通过免疫组织化学方法检测到 P-450HFLa。因此，本研究证实 P-450HFLa 并非胎儿特有，甚至在胎儿中也普遍存在。在绒毛合体滋养细胞中证实了 P-450HFLa 的显着阳性染色。相比之下，与许多其他胎盘抗原的情况不同，在食蟹猴胎盘中发现了 nop 阳性染色。这些发现初步得出P-450HFLa是人类特有的胎儿胎盘酶的结论。P-450HFLa被证实在妇科恶性肿瘤中频繁出现。所有妇科恶性肿瘤的平均阳性率为85%，而良性妇科疾病的阳性率为25%，表明P-450HFLa是致癌-teto-胎盘酶之一。我们利用亲和素-生物素-过氧化物酶反应建立了P-450HFLa的酶联免疫分析方法，并确定正常情况下范围>3.0单位/毫升。在妊娠第 4-42 周，P-450HFLa 水平范围为 0 至 38 单位/毫升。它在妊娠前三个月上升，在妊娠中期下降，在妊娠晚期再次上升。分娩后，血清P-450HFLa浓度立即恢复至非妊娠水平。良性卵巢肿瘤患者的阳性率为0%，子宫内膜异位症患者的阳性率为71%，子宫肌瘤患者的阳性率为10%。卵巢癌和子宫内膜癌患者的阳性率为100%。宫颈癌患者的阳性率为78%，但绝对值与健康非妊娠女性相比没有显着升高。目前的研究表明，这种酶可以用作无子宫内膜异位症患者妇科恶性肿瘤的新筛查标志物，但由于正常水平和病理水平之间的差异较小，因此不足以作为监测标志物。较少的