Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients.
BACKGROUND
Survivin, a member of the inhibitor of apoptosis-protein family suppresses apoptosis and regulates cell division. It is strongly overexpressed in the vast majority of cancers. We were interested if survivin detected by immunohistochemistry has prognostic relevance especially for patients of the two soft tissue sarcoma entities leiomyosarcoma and synovial sarcoma.


METHODS
Tumors of leiomyosarcoma (n = 24) and synovial sarcoma patients (n = 26) were investigated for their expression of survivin by immunohistochemistry. Survivin expression was assessed in the cytoplasm and the nucleus of tumor cells using an immunoreactive scoring system (IRS).


RESULTS
We detected a survivin expression (IRS > 2) in the cytoplasm of 20 leiomyosarcomas and 22 synovial sarcomas and in the nucleus of 12 leiomyosarcomas and 9 synovial sarcomas, respectively. There was no significant difference between leiomyosarcoma and synovial sarcoma samples in their cytoplasmic or nuclear expression of survivin. Next, all sarcoma patients were separated in four groups according to their survivin expression in the cytoplasm and in the nucleus: group 1: negative (IRS 0 to 2); group 2: weak (IRS 3 to 4); group 3: moderate (IRS 6 to 8); group 4: strong (IRS 9 to 12). In a multivariate Cox's regression hazard analysis survivin expression detected in the cytoplasm or in the nucleus was significantly associated with overall survival of patients in group 3 (RR = 5.7; P = 0.004 and RR = 5.7; P = 0.022, respectively) compared to group 2 (reference). Patients whose tumors showed both a moderate/strong expression of survivin in the cytoplasm and a moderate expression of survivin in the nucleus (in both compartments IRS > or = 6) possessed a 24.8-fold increased risk of tumor-related death (P = 0.003) compared to patients with a weak expression of survivin both in the cytoplasm and in the nucleus.


CONCLUSIONS
Survivin protein expression in the cytoplasma and in the nucleus detected by immunohistochemistry is significantly associated with prognosis of leiomyosarcoma and synovial sarcoma patients.
Taubert
Helge
H
Department of Oral and Maxillofacial Plastic Surgery, Martin-Luther-University Halle- Wittenberg, Halle, Germany. helge.taubert@medizin.uni-halle.de
Heidenreich
Chris
C
Holzhausen
Hans-Jürgen
HJ
Schulz
Antje
A
Bache
Matthias
M
Kappler
Matthias
M
Eckert
Alexander W
AW
Würl
Peter
P
Melcher
Ingo
I
Hauptmann
Kathrin
K
Hauptmann
Steffen
S
Schaser
Klaus-Dieter
KD
D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051034:Inhibitor of Apoptosis Proteins; D007890:Leiomyosarcoma / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D011379:Prognosis; D013584:Sarcoma, Synovial / Q000378:metabolism* / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000628:therapy; D000077022:Survivin; D016896:Treatment Outcome
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin