Apoptosis and apoptosis-related proteins (Fas, Fas ligand, Blc-2, p53) in lymphoid elements of human ovarian tumors.
Different types of lymphocytes have different roles in tumor suppression. Thus, their expression of apoptosis-related proteins (ARP - Fas and Fas ligand, bcl-2, p53) in lymphocytes and their apoptosis were analyzed immunohistochemically in ovarian tumors of different grades. Ovaries without oncologic disorders had few lymphocytes, mainly T cells, and no ARP. Benign cysts presented features of weak immune reaction: small lymphoid infiltration and few lymphocytes. The ARP were present in 13.7% to 23.5% of the lymphocytes, and apoptosis was rare. In borderline tumors, expansion of lymphoid infiltrates and increased density of lymphocytes resulted in a tenfold rise in total lymphocytes, reflecting intensification of the immune response. Most lymphocytes were T cells (92%) predominated by CD8+ cells that were in direct contact with tumor epithelial cells. ARP species were found in 47% to 65% of the lymphocytes, and apoptosis in 2.2%. In carcinomas with ligh lymphoid infiltration, lymphocytes were 2.5 times more abundant, and the apoptotic index as well as the number of CD20+ and CD25+ lymphocytes rose sharply, whereas bcl-2 positive lymphocytes decreased to 8% of their number in borderline tumors. In carcinomas with low lymphoid infiltration, the total lymphocyte count decreased eightfold compared to carcinomas with high lymphoid infiltration, reflecting the deep subcompensation of the lymphoid system. Few p53-positive lymphocytes were found in the carcinomas. In conclusion, we found a positive correlation between apoptosis and the numbers of CD4+ or CD8+ lymphocytes in epithelial ovarian tumors. This correlation could reflect the antitumor activity of T cells. However, the high expression of ARP studied by immune cells at the vicinity of the tumor ARP reveals the lymphoid vulnerability to apoptosis, resulting in devastation of the lymphoid tissue, and consequently in tumor progression.
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
Zinder
O
O
Tchanishev
R
R
Gershon
S
S
Mor
G
G
Zaltsman
Y
Y
Kohen
F
F
Zusman
I
I
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D017209:Apoptosis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D008024:Ligands; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*; D019014:fas Receptor / Q000032:analysis / Q000096:biosynthesis*
D015704:CD4 Antigens; D016827:CD8 Antigens; D008024:Ligands; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor