Survivin expression predicts poorer prognosis in anaplastic large-cell lymphoma.
OBJECTIVE
Survivin, a member of the inhibitor of apoptosis (IAP) family, is not detected in normal adult tissues but is overexpressed in various cancers, including some types of lymphoma. The frequency and prognostic significance of survivin expression in anaplastic large-cell lymphoma (ALCL) is unknown.


METHODS
We assessed for survivin expression in 62 ALCL tumors (30 anaplastic lymphoma kinase [ALK]-positive and 32 ALK-negative) obtained before doxorubicin-based chemotherapy. Given that survivin is a target of the STAT3 signaling pathway and STAT3 is activated in ALCL, survivin expression was also correlated with STAT3 activation.


RESULTS
Survivin was expressed in 34 tumors (55%) and did not correlate with ALK. A significant association between survivin expression and STAT3 activation was observed (P =.007, Fisher's exact test). For the ALK-positive group, the 5-year failure-free survival (FFS) was 34% for patients with survivin-positive ALCL compared with 100% for patients with survivin-negative ALCL (P =.009, log-rank test). For the ALK-negative group, the 5-year FFS was 46% for patients with survivin-positive tumors compared with 89% for patients with survivin-negative tumors (P =.03, log-rank test). Overall survival was similarly worse for patients with survivin-positive tumors in both the ALK-positive and ALK-negative groups. Furthermore, multivariate analysis confirmed the independent prognostic value of survivin expression, along with age older than 60 years and Ann Arbor stage III or IV.


CONCLUSIONS
Survivin is expressed in approximately half of ALCL tumors and independently predicts unfavorable clinical outcome. Modulation of survivin expression or function may provide a novel target for experimental therapy in patients with ALCL.
Schlette
Ellen J
EJ
Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Medeiros
L Jeffrey
LJ
Goy
Andre
A
Lai
Raymond
R
Rassidakis
George Z
GZ
D000209:Acute-Phase Proteins; D000328:Adult; D000367:Age Factors; D000077548:Anaplastic Lymphoma Kinase; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D015999:Multivariate Analysis; D009363:Neoplasm Proteins; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D016019:Survival Analysis; D000077022:Survivin; D015534:Trans-Activators / Q000032:analysis / Q000096:biosynthesis*
D000209:Acute-Phase Proteins; C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D015534:Trans-Activators; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases