Human astrocytomas co-expressing Fas and Fas ligand also produce TGF beta 2 and Bcl-2

Human astrocytomas frequently co-express Fas (APO-1/CD95) and Fas ligand (F asL), yet do not appear to be overly susceptible to suicidal, fratricidal a nd immune-mediated elimination. This suggests that these gliomas have acqui red mechanisms to prevent Fas-mediated apoptosis from occurring. Candidates for such a role include transforming growth factor-beta(2) (TGF beta 2) an d B-cell lymphoma/leukemia-2 (Bcl-2). TGF beta 2 effectively functions by h iding tumor cells from the immune system. This may potentially prevent the delivery of FasL from cytolytic T cells to Fas bearing astrocytomas. Bcl-2 works by rendering gliomas resistant to Fas-mediated apoptosis. Using immun ohistochemistry, we analyzed seventy-six human astrocytomas (11 World Healt h Organization (WHO) grade I, 17 grade II, 17 grade III, and 31 grade IV) f or the expression of Fas, FasL, (TGF beta(2)) and Bcl-2 in vivo. Positive i mmunoreactivity was found to significantly increase with increasing tumor g rade for Fas (p < 0.0002), FasL (p < 0.0001), TGF beta 2 (p < 0.001) and Bc l-2 (p < 0.01). In addition, Fas/FasL co-expression, a counter-intuitive co mbination of factors in regards to glioma survival, also increased with WHO grade. Forty-five of 76 (59%) astrocytomas co-expressed Fas and FasL. Of t hose co-expressing Fas and FasL, 44 of 45 (98%) produced TGF beta 2, and 26 of 45 (58%) expressed Bcl-2. We found a significant positive correlation b etween Fas/FasL co-expression and TGF beta 2 (p < 0.002) and Bcl-2 (p < 0.0 05) production. We conclude that Fas and FasL are frequently co-expressed i n human astrocytomas and these tumors are likely to produce other immunosup pressive and antiapoptotic factors such as TGF beta 2 and Bcl-2.