Apoptosis and apoptosis-related proteins (Fas, Fas ligand, bcl-2, p53) in macrophages of human ovarian epithelial tumors.
Apoptosis and the apoptosis-related proteins (ARP) (Fas, Fas ligand (FasL), bcl-2 and p53) were analyzed in macrophages of different human ovarian epithelial tumors. Few macrophages were found in ovaries of women without oncologic disorders. In ovarian benign cysts, macrophagic density reached 4.9+/-1.2 per 50,000 microm2, most were present in lymphoid-macrophagic infiltrates of the sub-epithelial stroma (3.7+/-0.5% of the area of a slide), and 23.4% were Fas and FasL positive. In borderline tumors, the expanse of lymphoid infiltrates increased to 15.6% of the area of a slide, and the number of macrophages increased 2.4-fold compared to benign cysts. Of the macrophages, 83-88% expressed Fas and FasL, few had bcl-2 and CD25 receptors, and isolated ones were apoptotic. In carcinomas with high lymphoid-macrophagic infiltration, the infiltrate occupied 17.5% of the slide and macrophages amounted to 12.1+/-1.5/50,000 microm2. Many macrophages were in regions of grouping apoptosis of tumor epithelial cells and significantly fewer expressed Fas, FasL and bcl-2. Macrophages destroyed by apoptosis accounted for 4.6%. In carcinomas with low lymphoid-macrophageal infiltration, the area of the last was 5.1% of the slide. There were 8.6+/-0.8 macrophages/50,000 microm2, mainly at the margins of zones of necrosis and of tumor cells' grouping apoptosis. Extensive macrophagic infiltration into tumor parenchyma is one way by which the host immune system destroys tumors. Fas and FasL appear in macrophages of benign cysts, but in borderline tumors and in carcinomas with low infiltration their concentration increases sharply, to 79.8% and 96.6%, respectively. In 4.5% of these cells, apoptosis of macrophages was seen. The findings suggest that macrophages participate in the transfer of ARP to tumor epithelial cells, thereby inducing their apoptosis, but undergoing the simultaneous apoptosis.
Ben-Hur
H
H
Department of Gynecology and Obstetrics, Kaplan Medical Center, Rehovot, Israel.
Gurevich
P
P
Ben-Arie
A
A
Huszar
M
M
Berman
V
V
Tendler
Y
Y
Tchanishev
R
R
Mor
G
G
Gershon
S
S
Zusman
I
I
D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018957:CD59 Antigens / Q000032:analysis*; D002277:Carcinoma / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000737:chemistry* / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000473:pathology*; D011336:Probability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D018957:CD59 Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53