Nuclear and cytoplasmic cellular distribution of survivin as survival predictor in resected non-small-cell lung cancer.
OBJECTIVE
Survivin is a member of the inhibitors of apoptosis (IAP) gene family that acts through pathways different from those involving the bcl-2 family. Largely undetectable in normal adult tissues, survivin is deregulated in most human cancers including non-small-cell lung cancer (NSCLC) and may represent a tumor marker with prognostic and therapeutic implications. Aim of our study was to determine the prognostic role of survivin as an apoptosis-related biomarker in a series of resected NSCLC patients.


METHODS
A retrospective series of resected NSCLC patients were retrieved from the files of the Regina Elena National Cancer Institute. Survivin was detected by immunohistochemistry (IHC) using a polyclonal antibody. Survivin displayed two kinds of immunoreactivity: (i) a diffuse cytoplasmic staining and (ii) a distinct nuclear staining. A score-scale to distinguish positive (score 1-2) vs. negative (score 0) pattern was applied. Clinical and biological (nuclear and cytoplasmic survivin staining) covariables were screened for a prognostic relationship with overall survival (OS) and disease-free survival (DFS) into the univariate and multivariate analyses.


RESULTS
Data referring to 116 NSCLC patients who underwent surgery for stage I-IIIA NSCLC were collected. Multivariate analyses identified tumor size, nodal status and nuclear, but not cytoplasmic, expression of survivin as significant independent predictors of OS, with a hazard ratio of 2.40 (95% CI 1.44, 3.99, p=0.001), 2.03 (95% CI 1.26, 3.26, p=0.003) and 1.83 (95% CI 1.01, 3.30, p=0.044), respectively. Median OS for nuclear survivin positive (score 1-2) and negative (score 0) patients were 23 months (95% CI 15, 31) and 36 months (95% CI 1, 76), respectively (p=0.01); five-year survival for score 1-2 and score 0 patients were 20% and 44.5%, respectively. Conversely, no significant impact on survival is found when patients are stratified according to cytoplasmic survivin expression.


CONCLUSIONS
Data presented herein open the issue that prognosis of stage I-IIIA NSCLC can be linked to the cellular pattern of distribution of survivin.
Bria
E
E
Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. emiliobria@yahoo.it
Visca
P
P
Novelli
F
F
Casini
B
B
Diodoro
M G
MG
Perrone-Donnorso
R
R
Botti
C
C
Sperduti
I
I
Facciolo
F
F
Milella
M
M
Cecere
F L
FL
Cognetti
F
F
Mottolese
M
M
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000601:surgery; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D012189:Retrospective Studies; D000077022:Survivin
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin