Immunohistochemical and immunoelectron microscopic study of cytochrome P-450 of human fetal livers (P-450HFLa): implications for an onco-feto-placental enzyme.
Cytochrome P-450 of human fetal livers (P-450HFLa) was demonstrated by the avidin-biotin immunoperoxidase technique in tissue samples as follows: human fetal organs, adult livers, human and cynomolgus placenta, and gynecologic organs which were obtained from 40 patients with gynecologic malignancies and 32 patients with benign diseases. P-450HFLa was clearly localized in the cytoplasm and membranes of the hepatocytes, and the fact was confirmed by an immunoelectron microscopic examination. In addition, a semiquantitative assay of staining intensity demonstrated that this enzyme tended to decrease with advancing age. These findings suggest that hepatic P-450HFLa synthesis is inversely proportional to age, and that this enzyme is one of the differentiation antigens. P-450HFLa was also detected immunohistochemically in other fetal organs. The present study thus confirms that P-450HFLa is not specific to the liver and is ubiquitous even in the fetus. Marked positive staining for P-450HFLa was demonstrated in villous syncytiotrophoblasts. In contrast, no positive staining was found in the cynomolgus-monkey placenta, unlike the case for many other placental antigens. These findings lead to the tentative conclusion that P-450HFLa is a feto-placental enzyme peculiar to humans. P-450HFLa was demonstrated to occur very frequently in gynecologic malignancies. The mean positivity rate for all gynecologic malignancies was 85%, while the rate was below 25% for benign gynecologic diseases, indicating that P-450HFLa is one of the onco-feto-placental enzymes. The present study thus suggests that this enzyme could be a promising new tumor marker for gynecologic malignancies.
Okajima
Y
Y
Department of Obstetrics and Gynecology, Faculty of Medicine, Chiba University, Japan.
Inaba
N
N
Fukazawa
I
I
Ota
Y
Y
Hirai
Y
Y
Sato
N
N
Yamamoto
G
G
Itahashi
K
K
Kitada
M
M
Kamataki
T
T
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D014408:Biomarkers, Tumor / Q000097:blood; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D005260:Female; D005333:Fetus / Q000201:enzymology; D005833:Genital Neoplasms, Female / Q000201:enzymology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D008252:Macaca fascicularis; D016253:Microscopy, Immunoelectron; D010920:Placenta / Q000201:enzymology*
D014408:Biomarkers, Tumor; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A