Apoptosis and apoptosis-related proteins in the epithelium of human ovarian tumors: immunohistochemical and morphometric studies.
BACKGROUND
The origin of malignant ovarian tumors is the subject of considerable controversy, which may be resolved by elucidation of molecular mechanisms of tumorigenesis. Therefore we have undertaken the study of apoptosis in these tumors.


METHODS
Apoptosis and the expression of its related proteins, Fas, Fas ligand (FasL), bcl-2 and p53, in epithelial cells of human ovarian tumors of different histological grades, were determined immunohistochemically and morphometrically.


RESULTS
Apoptosis-related proteins were absent from ovarian epithelia of patients afflicted with non-cancerous diseases. In ovarian tumors, the distribution of individual proteins varied, and depended on the grade and type of tumor. Fas and FasL were highly expressed in all tumors, while epithelial cells expressing bcl-2 were abundant in benign tumors, but their numbers significantly dwindled with the progression of malignancy. Cells expressing p53 were found in borderline tumors, and their numbers increased with malignancy, inverse of bcl-2 expression. Apoptotic tumor cells were scarce in borderline tumors and abundant in carcinomas. Grouping apoptosis was found in approximately 60% of the carcinomas.


CONCLUSIONS
The initial development of ovarian tumors is accompanied by high epithelial expression of Fas, FasL and bcl-2 proteins, while apoptosis and p53 proteins are detected only at later stages of tumorigenesis.
Ben-Hur
H
H
Department of Gynecology and Obstetrics, Kaplan Medical Center, Rehovot, Israel.
Gurevich
P
P
Huszar
M
M
Ben-Arie
A
A
Berman
V
V
Tendler
Y
Y
Tchanishev
R
R
Zinder
O
O
Mor
G
G
Zaltsman
Y
Y
Kohen
F
F
Zusman
I
I
D017209:Apoptosis; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology; D018293:Cystadenoma, Serous / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D008940:Mitotic Index; D010048:Ovarian Cysts / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011237:Predictive Value of Tests; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor