TY - JOUR
T1 - Nuclear and cytoplasmic cellular distribution of survivin as survival predictor in resected non-small-cell lung cancer
AU - Bria, E.
AU - Visca, P.
AU - Novelli, F.
AU - Casini, B.
AU - Diodoro, M. G.
AU - Perrone-Donnorso, R.
AU - Botti, C.
AU - Sperduti, I.
AU - Facciolo, F.
AU - Milella, M.
AU - Cecere, F. L.
AU - Cognetti, F.
AU - Mottolese, M.
PY - 2008/5
Y1 - 2008/5
N2 - Aim: 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.
AB - Aim: 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.
KW - Lung cancer
KW - Survival
KW - Survivin
UR - http://www.scopus.com/inward/record.url?scp=41949108454&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41949108454&partnerID=8YFLogxK
U2 - 10.1016/j.ejso.2007.06.002
DO - 10.1016/j.ejso.2007.06.002
M3 - Article
C2 - 17693049
AN - SCOPUS:41949108454
VL - 34
SP - 593
EP - 598
JO - European Journal of Surgical Oncology
JF - European Journal of Surgical Oncology
SN - 0748-7983
IS - 5
ER -