Elevated expression level of survivin protein in soft-tissue sarcomas is a strong independent predictor of survival.
OBJECTIVE
Survivin is a member of the inhibitor-of-apoptosis gene family and is known to be overexpressed in a number of tumor types. The aim of this study was to evaluate the prognostic value of survivin protein expression in tumor tissue extracts in a group of well-characterized soft-tissue sarcoma (STS) patients.


METHODS
In this investigation, malignant tissue samples from 63 STS patients as well as from a panel of tumor cell lines were investigated, with nonmalignant tissues serving as controls. The survivin protein level was quantified by a novel ELISA and by Western blot analysis. Results obtained by both methods were compared with clinicopathological parameters regarding tumor grade and tumor entity, and they were then correlated to survival in a multivariate Cox regression model.


RESULTS
High survivin levels were detected by ELISA and Western blot analysis in tumor tissue extracts and in lysates of tumor cell lines. None or only weak expression of survivin protein was found in nonmalignant cells and tissues. When comparing survivin values obtained by ELISA or Western blot, we found a significant correlation between both methods (P = 0.013, Pearson test). Our findings revealed that, in multivariate Cox regression analyses, survivin levels measured by ELISA and Western blot were significantly associated with tumor-related death in STS patients (P = 0.001, RR = 19.8, and P = 0.004, RR = 5.1, respectively). However, in a direct comparison of both survivin protein detection assays, we found a higher sensitivity and a stronger correlation to prognosis in survivin ELISA as compared with the Western blot assays. Furthermore, a higher tumor grade and more aggressive STS entity showed an elevated survivin protein expression level.


CONCLUSIONS
Altogether, an elevated survivin content in tumor tissue extracts has a significant and independent negative predictive value on the survival-rate of STS patients. This finding corresponds well to data obtained for the mRNA level of survivin, as shown previously (M. Kappler et al., Int. J. Cancer, 95: 360-363, 2001).
Kappler
Matthias
M
Institute of Pathology, University Halle-Wittenberg, Magdeburger Strasse 14, D-06097 Halle/Saale, Germany.
Kotzsch
Matthias
M
Bartel
Frank
F
Füssel
Susanne
S
Lautenschläger
Christine
C
Schmidt
Uta
U
Würl
Peter
P
Bache
Matthias
M
Schmidt
Hannelore
H
Taubert
Helge
H
Meye
Axel
A
D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D012509:Sarcoma / Q000378:metabolism* / Q000401:mortality*; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000401:mortality*; D000077022:Survivin; D013997:Time Factors; D014407:Tumor Cells, Cultured
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin