title: Fas expression in renal cell carcinoma accurately predicts patient survival after radical nephrectomy.
abstract: OBJECTIVE
  To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs).
  
  
  METHODS
  mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models.
  
  
  RESULTS
  A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator.
  
  
  CONCLUSIONS
  The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis.
authors.affiliation: Department of Surgery, Tottori University Faculty of Medicine, Yonago, Japan. sejimat @ grape.med.tottori-u.ac.jp
authors.forename: Takehiro
authors.initials: T
authors.lastname: Sejima
authors.forename: Shuichi
authors.initials: S
authors.lastname: Morizane
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hinata
authors.forename: Akihisa
authors.initials: A
authors.lastname: Yao
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Isoyama
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takenaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D016009:Chi-Square Distribution; D053222:Fas Ligand Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009392:Nephrectomy / Q000009:adverse effects / Q000401:mortality; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019014:fas Receptor / Q000032:analysis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019014:fas Receptor