Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms

Abstract

Summary Expression of apoptosis-related proteins, bcl-2, Bax, Fas and Fas ligand (L), in ovarian epithelial neoplasms together with its clinical relevance was examined by immunohistochemistry. They included 36 cases with adenoma, 33 with low potential malignancy (LPM) and 63 with carcinomas. bcl-2 expression was observed in 14 of 36 cases (39%) with adenoma, five of 33 (15%) with LPM ( P < 0.05) and 12 of 63 (19%) with carcinoma ( P < 0.05). Cases with bcl-2 expression showed more favourable prognosis than those without, but the difference was not statistically significant. There was no difference in frequency of Bax and Fas expression between each histologic category. Fas L expression was observed in one of 36 cases (3%) with adenoma, but in 12 of 33 (36%) with LPM ( P < 0.001) and 42 of 63 (67%) with carcinoma ( P < 0.0001). In carcinomas, cases expressing Fas L showed a less favourable prognosis than those without ( P = 0.02). Density of CD8+ lymphocytes, possibly cytotoxic T-cells, was higher in serous carcinoma with negative Fas L expression than those with positive Fas L expression. These findings suggest that Fas L expressing carcinomas induce apoptosis in infiltrating CTL with Fas expression, and escape from immune surveillance. © 2000 Cancer Research Campaign

EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes

“…Thus, reduced sensitivity to CD95-mediated apoptosis signals can conceivably lead to escape of virusinfected cells from immune surveillance. [17][18][19][20][21][22] Here we have found elevated levels of HGF and EGF in HBVinfected individuals and show that these growth factors stimulate survival signaling in primary human hepatocytes. Our findings support the notion that survival programs induced by EGF/HGF signaling may contribute to an apoptosis resistant phenotype in hepatocytes in the infected liver, thus contributing to immune escape and persistence of the viral infection.…”

Tumor-Infiltrating Macrophages Induce Apoptosis in Activated CD8+ T Cells by a Mechanism Requiring Cell Contact and Mediated by Both the Cell-Associated Form of TNF and Nitric Oxide

“…Apoptosis of infiltrating T cells in primary human tumors has been reported for several tumor types: ovarian (34,35), lung (36), breast (37), renal cell (38), and squamous cell carcinomas (39). FasL expression by tumor cells has recently been postulated to be the basis for TIL apoptosis because of the observations by several laboratories that primary tumors can express FasL (21).…”

The effects of FasL on inflammation and tumor survival are dependent on its expression levels

“…[1][2][3] FasL is expressed in the eye and testis where its pro-apoptotic activity, along with a variety of other immunosuppressive factors, is considered to contribute to the immune privilege status of these tissues. [3][4][5][6] FasL is also expressed by many human tumors and is associated with poor prognosis in breast, 7,8 ovarian 9 and liver 10 cancers, leading to the hypothesis that tumors use FasL to counterattack the tumorinfiltrating cytotoxic T cells and to escape the immune clearance. 11,12 In contrast to these observations, tumor cells engineered to express exogenous FasL triggered a potent neutrophil-mediated local inflammatory response and were rapidly rejected.…”