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Open Access Highly Accessed Research article

Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients

Helge Taubert1*, Chris Heidenreich1, Hans-Jürgen Holzhausen2, Antje Schulz3, Matthias Bache4, Matthias Kappler4, Alexander W Eckert1, Peter Würl5, Ingo Melcher3, Kathrin Hauptmann6, Steffen Hauptmann2 and Klaus-Dieter Schaser3

Author Affiliations

1 Department of Oral and Maxillofacial Plastic Surgery, Martin-Luther-University Halle- Wittenberg, Halle, Germany

2 Institute of Pathology, Martin-Luther-University Halle-Wittenberg, Halle, Germany

3 Section for Musculoskeletal Tumor Surgery, Center for Musculoskeletal Surgery, Charité - University Medicine, Berlin, Germany

4 Department of Radiotherapy, Martin-Luther-University Halle-Wittenberg, Halle, Germany

5 Malteser St. Franziskus Hospital gGmbH, Flensburg, Germany

6 Department of Pathology, Charité - University Medicine, Berlin, Germany

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BMC Cancer 2010, 10:65  doi:10.1186/1471-2407-10-65

Published: 24 February 2010

Abstract

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 ≥ 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.

Conclusion

Survivin protein expression in the cytoplasma and in the nucleus detected by immunohistochemistry is significantly associated with prognosis of leiomyosarcoma and synovial sarcoma patients.