Fas (APO-1/CD95) ligand and Fas expression in renal cell carcinomas - Correlation with the prognostic factors

Background and Objective.-Fas ligand (FasL, CD95L) is a type II transmembra ne protein of the tumor necrosis factor family that induces cells to send a n apoptotic signal to cells expressing Fas (CD95, APO-1). It has been shown that cancers have a dysregulated expression of Fas and FasL system, confer ring a survival advantage. It is important to understand FasL and Fas expre ssion in tumors, because the growth of cancer might be controlled by Fas-me diated apoptosis. Methods.-The expressions of FasL and Fas were studied by immunohistochemica l analyses in 51 cases of renal cell carcinomas and the adjacent normal ren al tissues, respectively. In addition, their expressions were compared with prognostic factors, such as tumor size, nuclear grade, TNM stage, and hist ologic types. Results.-In nonneoplastic renal tissues, FasL was expressed in all nephron segments, whereas Fas also expressed in all tubules, except for glomeruli. In renal cell carcinomas, FasL protein was detected in 50 (98.0%) of 51 cas es, whereas Fas expressed in 38 (74.5%) of 51 cases. In fact, the immunosta ining of Fas was less intense than that in the adjacent normal segments of all cases. The staining pattern showing both high expression of FasL and lo w expression of Fas was found in 36 (70.6%) (P = .04) of 51 cases, most of which were Fuhrman grade 2 or 3 tumors. However, the expression pattern did not correlate statistically with the tumor size, histologic type, or clini cal stage. On the other hand, most grade 4 tumors displayed high expression of both FasL and Fas (P < .001). Conclusion.-These data indicate that high expression of FasL and low expres sion of Fas protein in renal cell carcinomas may play a rose in evading sur veillance of the immune system. In addition, the FasL and Fas expressions a ppear to have a therapeutic implication for high-grade tumors rather than a prognostic one.