title: Nuclear localization of survivin is a positive prognostic factor for survival in advanced non-small-cell lung cancer.
abstract: BACKGROUND
  Expression of survivin, a member of the inhibitor of apoptosis protein family, is commonly detected in cancers but not in normal differentiated tissues. Survivin is usually localized in the cytoplasm of cancer cells, but nuclear localization has also been described, and we recently reported that survivin is a nuclear-cytoplasmic shuttling protein.
  
  
  METHODS
  Fifty-three tumor specimens from patients with inoperable non-small-cell lung cancer (NSCLC) (55% stage IIIA, 17% stage IIIB and 28% stage IV) who underwent chemotherapy treatment were evaluated with immunohistochemistry for survivin expression and localization. These two sets of data were processed and tested for correlation with major patient characteristics, response to chemotherapy, and overall and relapse-free survival.
  
  
  RESULTS
  Survivin was present only in malignant tissues, and 47/53 (89%) of the specimens were positive. The overall median expression of tumor cells was 40%, and this value was used as a cut-off point for statistical analysis. By dichotomizing the specimens as expressing low or high levels of survivin, a significant association was seen between the expression of survivin and the histology of the tumors (P=0.020), squamous cell carcinoma being the histotype with lower levels of survivin expression. Three patterns of localization were observed: 42% of cases (22/53) showed reactivity confined to the nucleus, 17% (nine of 53) only in the cytoplasm and 30% (16/53) in both the nucleus and the cytoplasm. Interestingly, nuclear survivin levels predicted longer overall and relapse-free survival, in univariate and multivariate analyses. Expression and localization of survivin did not correlate with response to chemotherapy.
  
  
  CONCLUSIONS
  Our results indicate that differential localization of survivin may be a prognostic factor for NSCLC. Further studies are warranted.
authors.affiliation: Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Vischioni
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: S W
authors.initials: SW
authors.lastname: Span
authors.forename: F A E
authors.initials: FA
authors.lastname: Kruyt
authors.forename: J A
authors.initials: JA
authors.lastname: Rodriguez
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002467:Cell Nucleus / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin