We have investigated whether the Fas-mediated cell death pathway is fu
nctional in renal cell carcinoma, The expression of Fas in surgical sp
ecimens and cell lines of renal cell carcinoma was examined. Fas expre
ssion was positive in six out of 18 tumors measured by flow cytometry
and was prominent in advanced tumors, Three out of the six Fas-positiv
e tumors had already metastasized at the time of surgery. A significan
t correlation was found between the tumor volume and the percentage of
Fas-positive cells in a tumor (r = 0.70, P = 0.0007), Fas-positive tu
mors were larger than Fas-negative tumors [mean tumor volume (ml) +/-
SD, Fas(+), 265.6 +/- 136.8; Fas(-), 65.8 +/- 80.9, P = 0.0012], All h
uman renal carcinoma cell lines tested (ACHN, Caki-1, SMKT-R-2, SMKT-R
-3 and SMKT-R-4) expressed Fas abundantly, as Fas-positive cells accou
nted for >50% in all cell lines by flow cytometry. Treatment with anti
-fas antibody caused apoptosis in Fas-positive renal cell carcinoma ce
ll lines, However, the effectiveness of apoptosis induction in individ
ual cell lines was not correlated with the level of Fas expressed, The
se data suggest that Fas targeting may be a therapeutic option for tre
atment of advanced renal cell carcinoma which is refractory to either
chemotherapy or irradiation.