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Published in: BMC Cancer 1/2010

Open Access 01-12-2010 | 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

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

Published in: BMC Cancer | Issue 1/2010

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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.
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Literature
1.
go back to reference Ferrari A, Gronchi A, Casanova M, Meazza C, Gandola L, Collini P, Lozza L, Bertulli R, Olmi P, Casali PG: Synovial sarcoma: a retrospective analysis of 271 patients of all ages at a single institution. Cancer. 2004, 101: 627-634. 10.1002/cncr.20386.CrossRefPubMed Ferrari A, Gronchi A, Casanova M, Meazza C, Gandola L, Collini P, Lozza L, Bertulli R, Olmi P, Casali PG: Synovial sarcoma: a retrospective analysis of 271 patients of all ages at a single institution. Cancer. 2004, 101: 627-634. 10.1002/cncr.20386.CrossRefPubMed
2.
go back to reference Velculescu VE, Madden SL, Zhang L, Lash AE, Yu J, Rago C, Lal A, Wang CJ, Beaudry GA, Ciriello KM, Cook BP, Dufault MR, Ferguson AT, Gao Y, He TC, Hermeking H, Hiraldo SK, Hwang PM, Lopez MA, Luderer HF, Mathews B, Petroziello JM, Polyak K, Zawel L, Kinzler KW: Analysis of human transcriptomes. Nat Genet. 1999, 23: 387-388. 10.1038/70487.CrossRefPubMed Velculescu VE, Madden SL, Zhang L, Lash AE, Yu J, Rago C, Lal A, Wang CJ, Beaudry GA, Ciriello KM, Cook BP, Dufault MR, Ferguson AT, Gao Y, He TC, Hermeking H, Hiraldo SK, Hwang PM, Lopez MA, Luderer HF, Mathews B, Petroziello JM, Polyak K, Zawel L, Kinzler KW: Analysis of human transcriptomes. Nat Genet. 1999, 23: 387-388. 10.1038/70487.CrossRefPubMed
3.
go back to reference Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC: Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998, 396: 580-584. 10.1038/25141.CrossRefPubMed Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC: Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998, 396: 580-584. 10.1038/25141.CrossRefPubMed
4.
go back to reference Li F, Ackermann EJ, Bennett CF, Rothermel AL, Plescia J, Tognin S, Villa A, Marchisio PC, Altieri DC: Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol. 1999, 1: 461-466. 10.1038/70242.CrossRefPubMed Li F, Ackermann EJ, Bennett CF, Rothermel AL, Plescia J, Tognin S, Villa A, Marchisio PC, Altieri DC: Pleiotropic cell-division defects and apoptosis induced by interference with survivin function. Nat Cell Biol. 1999, 1: 461-466. 10.1038/70242.CrossRefPubMed
5.
go back to reference Skoufias DA, Mollinari C, Lacroix FB, Margolis RL: Human survivin is a kinetochoreassociated passenger protein. J Cell Biol. 2000, 151: 1575-1582. 10.1083/jcb.151.7.1575.CrossRefPubMedPubMedCentral Skoufias DA, Mollinari C, Lacroix FB, Margolis RL: Human survivin is a kinetochoreassociated passenger protein. J Cell Biol. 2000, 151: 1575-1582. 10.1083/jcb.151.7.1575.CrossRefPubMedPubMedCentral
6.
go back to reference Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, Choo KH: Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr Biol. 2000, 10: 1319-1328. 10.1016/S0960-9822(00)00769-7.CrossRefPubMed Uren AG, Wong L, Pakusch M, Fowler KJ, Burrows FJ, Vaux DL, Choo KH: Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr Biol. 2000, 10: 1319-1328. 10.1016/S0960-9822(00)00769-7.CrossRefPubMed
7.
go back to reference Altieri DC: Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 2003, 3: 46-54. 10.1038/nrc968.CrossRefPubMed Altieri DC: Validating survivin as a cancer therapeutic target. Nat Rev Cancer. 2003, 3: 46-54. 10.1038/nrc968.CrossRefPubMed
8.
go back to reference Brabletz S, Schmalhofer O, Brabletz T: Gastrointestinal stem cells in development and cancer. J Pathol. 2009, 217: 307-317. 10.1002/path.2475.CrossRefPubMed Brabletz S, Schmalhofer O, Brabletz T: Gastrointestinal stem cells in development and cancer. J Pathol. 2009, 217: 307-317. 10.1002/path.2475.CrossRefPubMed
9.
go back to reference Kappler M, Kotzsch M, Bartel F, Füssel S, Lautenschläger C, Schmidt U, Würl P, Bache M, Schmidt H, Taubert H, Meye A: Elevated expression level of survivin protein in soft-tissue sarcomas is a strong independent predictor of survival. Clin Cancer Res. 2003, 9: 1098-1104.PubMed Kappler M, Kotzsch M, Bartel F, Füssel S, Lautenschläger C, Schmidt U, Würl P, Bache M, Schmidt H, Taubert H, Meye A: Elevated expression level of survivin protein in soft-tissue sarcomas is a strong independent predictor of survival. Clin Cancer Res. 2003, 9: 1098-1104.PubMed
10.
go back to reference Li F, Yang J, Ramnath N, Javle MM, Tan D: Nuclear or cytoplasmic expression of survivin: what is the significance?. Int J Cancer. 2005, 114: 509-512. 10.1002/ijc.20768.CrossRefPubMedPubMedCentral Li F, Yang J, Ramnath N, Javle MM, Tan D: Nuclear or cytoplasmic expression of survivin: what is the significance?. Int J Cancer. 2005, 114: 509-512. 10.1002/ijc.20768.CrossRefPubMedPubMedCentral
11.
go back to reference Trieb K, Lehner R, Stulnig T, Sulzbacher I, Shroyer KR: Survivin expression in human osteosarcoma is a marker for survival. Eur J Surg Oncol. 2003, 29: 379-382. 10.1053/ejso.2002.1415.CrossRefPubMed Trieb K, Lehner R, Stulnig T, Sulzbacher I, Shroyer KR: Survivin expression in human osteosarcoma is a marker for survival. Eur J Surg Oncol. 2003, 29: 379-382. 10.1053/ejso.2002.1415.CrossRefPubMed
12.
go back to reference Wang W, Luo H, Wang A: Expression of survivin and correlation with PCNA in osteosarcoma. J Surg Oncol. 2006, 93: 578-584. 10.1002/jso.20507.CrossRefPubMed Wang W, Luo H, Wang A: Expression of survivin and correlation with PCNA in osteosarcoma. J Surg Oncol. 2006, 93: 578-584. 10.1002/jso.20507.CrossRefPubMed
13.
go back to reference Clark JC, Dass CR, Choong PF: A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008, 134: 281-297. 10.1007/s00432-007-0330-x.CrossRefPubMed Clark JC, Dass CR, Choong PF: A review of clinical and molecular prognostic factors in osteosarcoma. J Cancer Res Clin Oncol. 2008, 134: 281-297. 10.1007/s00432-007-0330-x.CrossRefPubMed
14.
go back to reference Kappler M, Köhler T, Kampf C, Diestelkötter P, Würl P, Schmitz M, Bartel F, Lautenschläger C, Rieber EP, Schmidt H, Bache M, Taubert H, Meye A: Increased survivin transcript levels: an independent negative predictor of survival in soft tissue sarcoma patients. Int J Cancer. 2001, 95: 360-363. 10.1002/1097-0215(20011120)95:6<360::AID-IJC1063>3.0.CO;2-1.CrossRefPubMed Kappler M, Köhler T, Kampf C, Diestelkötter P, Würl P, Schmitz M, Bartel F, Lautenschläger C, Rieber EP, Schmidt H, Bache M, Taubert H, Meye A: Increased survivin transcript levels: an independent negative predictor of survival in soft tissue sarcoma patients. Int J Cancer. 2001, 95: 360-363. 10.1002/1097-0215(20011120)95:6<360::AID-IJC1063>3.0.CO;2-1.CrossRefPubMed
15.
go back to reference Taubert H, Würl P, Greither T, Kappler M, Bache M, Bartel F, Kehlen A, Lautenschläger C, Harris LC, Kaushal D, Füssel S, Meye A, Böhnke A, Schmidt H, Holzhausen HJ, Hauptmann S: Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients. Oncogene. 2007, 26: 7170-7174. 10.1038/sj.onc.1210530.CrossRefPubMed Taubert H, Würl P, Greither T, Kappler M, Bache M, Bartel F, Kehlen A, Lautenschläger C, Harris LC, Kaushal D, Füssel S, Meye A, Böhnke A, Schmidt H, Holzhausen HJ, Hauptmann S: Stem cell-associated genes are extremely poor prognostic factors for soft-tissue sarcoma patients. Oncogene. 2007, 26: 7170-7174. 10.1038/sj.onc.1210530.CrossRefPubMed
16.
go back to reference Caldas H, Holloway MP, Hall BM, Qualman SJ, Altura RA: Survivin-directed RNA interference cocktail is a potent suppressor of tumour growth in vivo. J Med Genet. 2006, 43: 119-128. 10.1136/jmg.2005.034686.CrossRefPubMed Caldas H, Holloway MP, Hall BM, Qualman SJ, Altura RA: Survivin-directed RNA interference cocktail is a potent suppressor of tumour growth in vivo. J Med Genet. 2006, 43: 119-128. 10.1136/jmg.2005.034686.CrossRefPubMed
17.
go back to reference Tabone-Eglinger S, Bahleda R, Côté JF, Terrier P, Vidaud D, Cayre A, Beauchet A, Théou-Anton N, Terrier-Lacombe MJ, Lemoine A, Penault-Llorca F, Le Cesne A, Emile JF: Frequent EGFR Positivity and Overexpression in High-Grade Areas of Human MPNSTs. Sarcoma. 2008, 2008: 10.1155/2008/849156. Article ID 849156 Tabone-Eglinger S, Bahleda R, Côté JF, Terrier P, Vidaud D, Cayre A, Beauchet A, Théou-Anton N, Terrier-Lacombe MJ, Lemoine A, Penault-Llorca F, Le Cesne A, Emile JF: Frequent EGFR Positivity and Overexpression in High-Grade Areas of Human MPNSTs. Sarcoma. 2008, 2008: 10.1155/2008/849156. Article ID 849156
18.
go back to reference Van Unnik JA, Coindre JM, Contesso G, Albus-Lutter CE, Schiodt T, Sylvester R, Thomas D, Bramwell V, Mouridsen HT: Grading of Soft Tissue Sarcomas: Experience of the EORTC Soft and Bone Sarcoma Group. Eur J Cancer. 1993, 29A: 2089-2093. 10.1016/0959-8049(93)90039-I.CrossRefPubMed Van Unnik JA, Coindre JM, Contesso G, Albus-Lutter CE, Schiodt T, Sylvester R, Thomas D, Bramwell V, Mouridsen HT: Grading of Soft Tissue Sarcomas: Experience of the EORTC Soft and Bone Sarcoma Group. Eur J Cancer. 1993, 29A: 2089-2093. 10.1016/0959-8049(93)90039-I.CrossRefPubMed
19.
go back to reference Wittekind C, Meyer HJ, Bootz F: UICC TNM Klassifikation maligner Tumoren. 2002, Springer-Verlag, Berlin, Heidelberg, New York, 152-156. 6 Wittekind C, Meyer HJ, Bootz F: UICC TNM Klassifikation maligner Tumoren. 2002, Springer-Verlag, Berlin, Heidelberg, New York, 152-156. 6
20.
go back to reference Bache M, Reddemann R, Said HM, Holzhausen HJ, Taubert H, Becker A, Kuhnt T, Hänsgen G, Dunst J, Vordermark D: Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1alpha-related markers, and hemoglobin levels. Int J Radiat Oncol Biol Phys. 2006, 66: 1481-1487.CrossRefPubMed Bache M, Reddemann R, Said HM, Holzhausen HJ, Taubert H, Becker A, Kuhnt T, Hänsgen G, Dunst J, Vordermark D: Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1alpha-related markers, and hemoglobin levels. Int J Radiat Oncol Biol Phys. 2006, 66: 1481-1487.CrossRefPubMed
21.
go back to reference Eckert AW, Lautner MH, Taubert H, Schubert J, Bilkenroth U: Expression of Glut-1 is a prognostic marker for oral squamous cell carcinoma patients. Oncol Rep. 2008, 20: 1381-1385.PubMed Eckert AW, Lautner MH, Taubert H, Schubert J, Bilkenroth U: Expression of Glut-1 is a prognostic marker for oral squamous cell carcinoma patients. Oncol Rep. 2008, 20: 1381-1385.PubMed
22.
go back to reference Remmele W, Stegner HE: Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987, 8: 138-140.PubMed Remmele W, Stegner HE: Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987, 8: 138-140.PubMed
23.
go back to reference Engels K, Knauer SK, Metzler D, Simf C, Struschka O, Bier C, Mann W, Kovács AF, Stauber RH: Dynamic intracellular survivin in oral squamous cell carcinoma: underlying molecular mechanism and potential as an early prognostic marker. J Pathol. 2007, 211: 532-540. 10.1002/path.2134.CrossRefPubMed Engels K, Knauer SK, Metzler D, Simf C, Struschka O, Bier C, Mann W, Kovács AF, Stauber RH: Dynamic intracellular survivin in oral squamous cell carcinoma: underlying molecular mechanism and potential as an early prognostic marker. J Pathol. 2007, 211: 532-540. 10.1002/path.2134.CrossRefPubMed
24.
go back to reference Ryan BM, O'Donovan N, Duffy MJ: Survivin: a new target for anti-cancer therapy. Cancer Treat Rev. 2009, 35: 553-562. 10.1016/j.ctrv.2009.05.003.CrossRefPubMed Ryan BM, O'Donovan N, Duffy MJ: Survivin: a new target for anti-cancer therapy. Cancer Treat Rev. 2009, 35: 553-562. 10.1016/j.ctrv.2009.05.003.CrossRefPubMed
25.
go back to reference Honma I, Kitamura H, Torigoe T, Takahashi A, Tanaka T, Sato E, Hirohashi Y, Masumori N, Tsukamoto T, Sato N: Phase I clinical study of anti-apoptosis protein survivin- derived peptide vaccination for patients with advanced or recurrent urothelial cancer. Cancer Immunol Immunother. 2009, 58: 1801-1807. 10.1007/s00262-009-0691-x.CrossRefPubMed Honma I, Kitamura H, Torigoe T, Takahashi A, Tanaka T, Sato E, Hirohashi Y, Masumori N, Tsukamoto T, Sato N: Phase I clinical study of anti-apoptosis protein survivin- derived peptide vaccination for patients with advanced or recurrent urothelial cancer. Cancer Immunol Immunother. 2009, 58: 1801-1807. 10.1007/s00262-009-0691-x.CrossRefPubMed
26.
go back to reference Kobayashi J, Torigoe T, Hirohashi Y, Idenoue S, Miyazaki A, Yamaguchi A, Hiratsuka H, Sato N: Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant survivin- 2B in oral cancer patients. J Transl Med. 2009, 7: 1-11. 10.1186/1479-5876-7-1.CrossRefPubMedPubMedCentral Kobayashi J, Torigoe T, Hirohashi Y, Idenoue S, Miyazaki A, Yamaguchi A, Hiratsuka H, Sato N: Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant survivin- 2B in oral cancer patients. J Transl Med. 2009, 7: 1-11. 10.1186/1479-5876-7-1.CrossRefPubMedPubMedCentral
Metadata
Title
Expression of survivin detected by immunohistochemistry in the cytoplasm and in the nucleus is associated with prognosis of leiomyosarcoma and synovial sarcoma patients
Authors
Helge Taubert
Chris Heidenreich
Hans-Jürgen Holzhausen
Antje Schulz
Matthias Bache
Matthias Kappler
Alexander W Eckert
Peter Würl
Ingo Melcher
Kathrin Hauptmann
Steffen Hauptmann
Klaus-Dieter Schaser
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2010
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-10-65

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