[The evaluation of Fas/Fas ligand system in renal cell carcinoma--the effect of preoperative interferon-alpha therapy].
OBJECTIVE
In order to investigate the effect of preoperative interferon (IFN)-alpha on Fas/Fas ligand (FasL) system, we examined Fas and FasL expression and the occurrence of apoptotic cell death in a preoperative therapy group, and in a control group using surgically resected renal cell carcinoma (RCC) tissues.


METHODS
Ten cases were served as the preoperative therapy group, and sixteen cases as the control group. IFN-alpha was administered at five megaunits daily intramuscularly for two weeks in the preoperative therapy group. Immunohistochemistry for Fas and FasL, and terminal-deoxynucleotidyl-transferase (TdT)-mediated digoxigenin-dUTP nick end-labeling (TUNEL) were employed. We defined the labeling index (LI) as percentage of Fas- or FasL-positive cells in carcinomatous cells, and apoptotic index (AI) as percentage of TUNEL-positive cells in carcinomatous cells.


RESULTS
Significant correlations were found between the LIs of Fas and AIs in all 26 cases. LIs of Fas and AIs of the preoperative therapy group were significantly higher than those of the control group. FasL expression was detected in nine out of ten cases in the preoperative therapy group, and in fourteen out of sixteen cases in the control group. There were no significant differences in LIs of FasL between two groups.


CONCLUSIONS
These data suggest that apoptosis via the Fas/FasL system is functional, and that preoperative IFN-alpha treatment may up-regulate the Fas/FasL system in RCC. On the other hand, we need to investigate about an immune-escape mechanism through the FasL expression considering the relatively frequent expression of FasL in our results in RCC from now.
Sejima
T
T
Department of Urology, Tottori University School of Medicine.
Miyagawa
I
I
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D016898:Interferon-alpha / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015398:Signal Transduction; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D019014:fas Receptor