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

Helge Taubert,Steffen Hauptmann,Chris Heidenreich,Antje Schulz,Ingo Melcher,Klaus-Dieter Schaser,Peter Würl,Matthias Kappler,Hans-Jürgen Holzhausen,Kathrin Hauptmann,Alexander W Eckert,Matthias Bache

doi:10.1186/1471-2407-10-65

Abstract

BackgroundSurvivin, 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.MethodsTumors 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).ResultsWe 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.ConclusionSurvivin protein expression in the cytoplasma and in the nucleus detected by immunohistochemistry is significantly associated with prognosis of leiomyosarcoma and synovial sarcoma patients.

Highlights

Survivin, a member of the inhibitor of apoptosis-protein family suppresses apoptosis and regulates cell division
We detected in the synovial sarcoma samples (n = 26) a survivin expression that was negative, weak, moderate or strong in four, six, nine and seven cases in the cytoplasm and that was negative, weak or moderate in 17, two or seven cases, respectively (Table 1; Fig.1)
The number of more strongly stained specimens is somewhat higher for synovial sarcomas there was no significant difference in survivin expression between leiomyosarcomas and synovial sarcomas

Summary

Introduction

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. These survival rates did only tend to result in better outcomes if chemotherapy was performed; clearly underscoring the absolute need for identification of prognostic relevant factors. These factors, possibly assisting in prediction of disease specific prognosis, may help to evaluate the risk for local and systemic recurrence and allow stratifying patients to different treatment strategies.

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