Loss of CD95 expression is linked to most but not all p53 mutants in European hepatocellular carcinoma

Experimental data have shown p53-dependent CD95 induction to be associated with increased levels of apoptosis after cytostatic treatment in hepatoma c ells. A study of Japanese hepatocellular carcinoma (HCC) has reported an in verse correlation between CD95 and p53 expression. To examine the interacti on of p53 and CD95 in tumors we investigated which alterations in p53 can b e linked to loss of CD95 expression in European HCC. In 39 tumors we analyz ed CD95 by immunohistochemistry and assessed the correlation between the fi ndings of the p53 status as determined by immunohistochemistry and single-s trand conformation polymorphism with polymerase chain reaction sequencing. In 10 of 14 tumors with evidence of p53 aberration there was also loss of C D95 expression, compared to 6 of 25 samples with apparent wild-type p53 (P < 0.01). Three tumors with p53 mutations but sustained CD95 expression show ed single base substitutions mapping to a narrow region of 20 codons in p53 . A significant correlation with differentiation status of the tumor was fo und for the p53 aberration but not for CD95 expression. This is the first s tudy to link loss of CD95 expression to specific p53 alterations in HCC. Fu nctional p53 appears to be a major factor for CD95 expression in hepatocyte s, the loss of which could contribute to chemoresistance and possibly immun e evasion in hepatocellular carcinoma. Sustained CD95 expression in tumors with certain p53 aberrations may indicate functional heterogeneity of p53 m utants.