title: The clinical effect of the inhibitor of apopotosis protein livin in melanoma.
abstract: OBJECTIVE
  The inhibitor of apoptosis protein (IAP) livin is frequently overexpressed in melanoma. Livin binds caspases and thereby inhibits apoptosis. We found that caspases cleave livin to produce a truncated form with a paradoxical proapoptotic activity.
  
  
  METHODS
  We assessed the correlation of livin expression with survival among 114 melanoma patients treated with an autologous melanoma vaccine. In 52 patients, resection resulted in no evidence of disease (NED) and 62 remained with active disease (WAD). Protein levels were assessed using Western blot.
  
  
  RESULTS
  We found livin protein expression in 44/114 samples (38.4%). Median overall survival was 1.4 years in NED patients with high levels of livin protein, 8.4 years in those with low-intermediate levels and not reached in patients who did not express livin (p = 0.025). The corresponding overall survival was 2.3 years among WAD patients with high levels of livin protein, 11.3 years in those with low-intermediate levels and, paradoxically, only 4.0 years in patients who did not express livin (p = 0.012).
  
  
  CONCLUSIONS
  Livin protein expression may play a role in the progression of melanoma and correlates with survival. A high level of the protein is associated with a poor prognosis. However, in WAD patients low to intermediate level of livin, rather than absence of the protein, is associated with a favorable prognosis. This is probably due to the paradoxical proapoptotic activity of this important regulator of apoptosis.
authors.affiliation: Department of Hematology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Lazar
authors.forename: Riki
authors.initials: R
authors.lastname: Perlman
authors.forename: Michal
authors.initials: M
authors.lastname: Lotem
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
authors.forename: Dina
authors.initials: D
authors.lastname: Ben-Yehuda
authors.forename: Luna
authors.initials: L
authors.lastname: Kadouri
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D019496:Cancer Vaccines; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis*; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000628:therapy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011237:Predictive Value of Tests; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000628:therapy; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins