Skip to main content

Survivin expression in head and neck squamous cell carcinomas is frequent and correlates with clinical parameters and treatment outcomes

Clinical Oral Investigations volume 23, pages 361–367 (2019)Cite this article

Abstract

Objectives

Strong expression of survivin is associated with worse survival in many different tumours, and in cell culture, a correlation between radiation resistance and survivin expression can be seen. The potential of survivin expression as a prognostic/predictive marker or therapeutic target has not been examined in head and neck squamous cell carcinomas (HNSCC) yet.

Material and methods

Retrospective study of 452 tissue samples and clinical data from patients with squamous cell carcinomas of the larynx/hypopharynx (LSCC), oral cavity (OSCC) and oropharynx (OPSCC) treated in the University Medical Centre Hamburg-Eppendorf between 2002 and 2006. The expression patterns were detected by tissue microarray technique and correlated with clinical parameters (sex, age, tumour location, TNM 7th edition, grading, recurrence-free and overall survival).

Results

222 OSCC, 126 OPSCC and 105 LSCC tumours of 118 females and 335 males with a mean follow-up of 41.3 months were examined. Survivin expression correlates with pN, cM, pT and overall survival.

Conclusion and clinical relevance

The potential of survivin as a prognostic/predictive marker is very high. The findings have to be confirmed in a larger cohort of HNSCC esp. in those tumours treated primarily with radio/radiochemotherapy.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Hunter KD, Parkinson EK, Harrison PR (2005) Profiling early head and neck cancer. Nat Rev Cancer 5(2):127–135

    Article  Google Scholar 

  2. Parkin DM, Lӓӓrӓ E, Muir CS (1988) Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer 41(2):184–197

    Article  PubMed  Google Scholar 

  3. Ragin CC, Modugno F, Gollin SM (2007) The epidemiology and risk factors of head and neck cancer: a focus on human papillomavirus. J Dent Res 86(2):104–114

    Article  PubMed  Google Scholar 

  4. Sharma H, Sen S, Mathur M, Bahadur S, Singh N (2004) Combined evaluation of expression of telomerase, survivin, and anti-apoptotic Bcl-2 family members in relation to loss of differentiation and apoptosis in human head and neck cancers. Head Neck 26(8):733–740

    Article  PubMed  Google Scholar 

  5. Pickhard A, Grӧber S, Haug AK et al (2014) Survivin and pAkt as potential prognostic markers in squamous cell carcinoma of the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol 117(6):733–742

    Article  PubMed  Google Scholar 

  6. Farnebo L, Tiefenbӧck K, Ansell A, Thunell LK, Garvin S, Roberg K (2013) Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients. Int J Cancer 133(8):1994–2003

    Article  PubMed  Google Scholar 

  7. Lippert BM, Knauer SK, Fetz V, Mann W, Stauber RH (2007) Dynamic survivin in head and neck cancer: molecular mechanism and therapeutic potential. Int J Cancer 121(6):1169–1174

    Article  PubMed  Google Scholar 

  8. Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3(8):917–921

    Article  PubMed  Google Scholar 

  9. Marioni G, D’Alessandro E, Bertolin A, Staffieri A (2010) Survivin multifaceted activity in head and neck carcinoma: current evidence and future therapeutic challenges. Acta Otolaryngol 130(1):4–9

    Article  PubMed  Google Scholar 

  10. Scheper MA, Nikitakis NG, Sauk JJ (2007) Survivin is a downstream target and effector of sulindac-sensitive oncogenic Stat3 signalling in head and neck cancer. Int J Oral Maxillofac Surg 36(7):632–639

    Article  PubMed  Google Scholar 

  11. Cui M, Au JL, Wientjes MG, O’Donnell MA, Loughlin KR, Lu Z (2015) Intravenous siRNA silencing of survivin enhances activity of mitomycin C in human bladder RT4 xenografts. J Urol 194(1):230–237

    Article  PubMed  PubMed Central  Google Scholar 

  12. Gibbons JA, Kanwar JR, Kanwar RK (2015) Iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer. BMC Cancer 15:425

    Article  PubMed  PubMed Central  Google Scholar 

  13. Adamkov M, Výbohová D, Tupá V, Chylíková J, Horáček J, Benčat M (2015) Expression and significance of survivin in colorectal high grade and low grade adenomas. Acta Histochem 117(6):590–594

    Article  PubMed  Google Scholar 

  14. Phatak P, Byrnes KA, Mansour D, Liu L, Cao S, Li R, Rao JN, Turner DJ, Wang JY, Donahue JM (2016) Overexpression of miR-214-3p in esophageal squamous cancer cells enhances sensitivity to cisplatin by targeting survivin directly and indirectly through CUG-BP1. Oncogene 35(16):2087–2097

    Article  PubMed  Google Scholar 

  15. Lu CD, Altieri DC, Tanigawa N (1998) Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer Res 58(9):1808–1812

    PubMed  Google Scholar 

  16. Ezponda T, Pajares MJ, Agorreta J, Echeveste JI, Lopez-Picazo JM, Torre W, Pio R, Montuenga LM (2010) The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing survivin expression. Clin Cancer Res 16(16):4113–4125

    Article  PubMed  Google Scholar 

  17. Yip KW, Shi W, Pintilie M, Martin JD, Mocanu JD, Wong D, MacMillan C, Gullane P, O’Sullivan B, Bastianutto C, Liu FF (2006) Prognostic significance of the Epstein-Barr virus, p53, Bcl-2, and survivin in nasopharyngeal cancer. Clin Cancer Res 12(19):5726–5732

    Article  Google Scholar 

  18. Yi XP, Han T, Li YX, Long XY, Li WZ (2015) Simultaneous silencing of XIAP and survivin causes partial mesenchymal-epithelial transition of human pancreatic cancer cells via the PTEN/PI3K/Akt pathway. Mol Med Rep 12(1):601–608

    Article  PubMed  Google Scholar 

  19. Cavalieri F, Beretta GL, Cui J, Braunger JA, Yan Y, Richardson JJ, Tinelli S, Folini M, Zaffaroni N, Caruso F (2015) Redox-sensitive PEG-polypeptide nanoporous particles for survivin silencing in prostate cancer cells. Biomacromolecules 16(7):2168–2178

    Article  PubMed  Google Scholar 

  20. Lin CK, Chao TK, Yu CP, Yu MH, Jin JS (2009) The expression of six biomarkers in the four most common ovarian cancers: correlation with clinicopathological parameters. APMIS 117(3):162–175

    Article  PubMed  Google Scholar 

  21. Krambeck AE, Dong H, Thompson RH, Kuntz SM, Lohse CM, Leibovich BC, Blute ML, Sebo TJ, Cheville JC, Parker AS, Kwon ED (2007) Survivin and b7-h1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma. Clin Cancer Res 13(6):1749–1756

    Article  PubMed  Google Scholar 

  22. Labarrade F, Bergeron L, Serre C, Lebleu A, Busuttil V, Botto JM, Domloge N (2015) Modulating the expression of survivin and other basal epidermal proteins protects human skin from UVB damage and oxidative stress. J Cosmet Dermatol 14(3):191–203

    Article  PubMed  Google Scholar 

  23. Fukuda S, Pelus LM (2006) Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther 5(5):1087–1098

    Article  PubMed  Google Scholar 

  24. Yamamoto T, Manome Y, Nakamura M, Tanigawa N (2002) Downregulation of survivin expression by induction of the effector cell protease receptor-1 reduces tumor growth potential and results in an increased sensitivity to anticancer agents in human colon cancer. Eur J Cancer 38(17):2316–2324

    Article  PubMed  Google Scholar 

  25. Khan Z, Khan N, Tiwari RP, Patro IK, Prasad GB, Bisen PS (2010) Down-regulation of survivin by oxaliplatin diminishes radioresistance of head and neck squamous carcinoma cells. Radiother Oncol 96(2):267–273

    Article  PubMed  Google Scholar 

  26. Khan Z, Tiwari RP, Mulherkar R, Sah NK, Prasad GBKS, Shrivastava BR, Bisen PS (2009) Detection of survivin and p53 in human oral cancer: correlation with clinicopathologic findings. Head Neck 31(8):1039–1048

    Article  PubMed  Google Scholar 

  27. Mita AC, Mita MM, Nawrocki ST, Giles FJ (2008) Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics. Clin Cancer Res 14(16):5000–5005

    Article  PubMed  Google Scholar 

  28. Jaiswal PK, Goel A, Mittal RD (2015) Survivin: a molecular biomarker in cancer. Indian J Med Res 141(4):389–397

    Article  PubMed  PubMed Central  Google Scholar 

  29. Waligórska-Stachura J, Jankowska A, Waśko R, Liebert W, Biczysko M, Czarnywojtek A, Baszko-Błaszyk D, Shimek V, Ruchała M (2012) Survivin—prognostic tumor biomarker in human neoplasms—review. Ginekol Pol 83(7):537–540

    PubMed  Google Scholar 

  30. Bubendorf L, Kononen J, Koivisto P, Schraml P, Moch H, Gasser TC, Willi N, Mihatsch MJ, Sauter G, Kallioniemi OP (1999) Survey of gene amplifications during prostate cancer progression by high-throughput fluorescence in situ hybridization on tissue microarrays. Cancer Res 59(4):803–806

    PubMed  Google Scholar 

  31. Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45(4–5):309–316

    Article  PubMed  PubMed Central  Google Scholar 

  32. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90

    Article  PubMed  PubMed Central  Google Scholar 

  33. Thomas GR, Nadiminti H, Regalado J (2005) Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. Int J Exp Pathol 86(6):347–363

    Article  PubMed  PubMed Central  Google Scholar 

  34. Funk GF, Karnell LH, Robinson RA, Zhen WK, Trask DK, Hoffman HT (2002) Presentation, treatment, and outcome of oral cavity cancer: a National Cancer Data Base report. Head Neck 24(2):165–180

    Article  PubMed  Google Scholar 

  35. Marioni G, Bertolin A, Giacomelli L, Marchese-Ragona R, Savastano M, Calgaro N, Marino F, de Filippis C, Staffieri A (2006) Expression of the apoptosis inhibitor protein survivin in primary laryngeal carcinoma and cervical lymph node metastasis. Anticancer Res 26(5B):3813–3817

    PubMed  Google Scholar 

  36. Khan Z, Khan AA, Prasad G, Khan N, Tiwari RP, Bisen PS (2016) Growth inhibition and chemo-radiosensitization of head and neck squamous cell carcinoma (HNSCC) by survivin-siRNA lentivirus. Radiother Oncol 118(2):359–368

    Article  PubMed  Google Scholar 

  37. Sobin LH, Fleming ID (1997) TNM classification of malignant tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 80(9):1803–1804

    Article  PubMed  Google Scholar 

  38. Zhang L, Zhang W, Wang Y-F, Liu B, Zhang WF, Zhao YF, Kulkarni AB, Sun ZJ (2015) Dual induction of apoptotic and autophagic cell death by targeting survivin in head and neck squamous cell carcinoma. Cell Death Dis 6:e1771

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The work was supported by the Institute of Pathology and the Department of Otolaryngology, Head and Neck Surgery at the University Medical Centre Hamburg-Eppendorf.

Author information

Affiliations

  1. Department of Otolaryngology, Head and Neck Surgery, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Adrian Münscher, Sebastian Prochnow & Arne Böttcher

  2. Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Amit Gulati

  3. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Guido Sauter & Till Sebastian Clauditz

  4. Department of Otorhinolaryngology, Head and Neck Surgery, Asklepios Altona Hospital, Hamburg, Germany

    Balazs Lörincz

  5. Department of Plastic, Reconstructive and Aesthetic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Marco Blessmann

  6. Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Henning Hanken

Authors
  1. Adrian Münscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sebastian Prochnow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amit Gulati
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guido Sauter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Balazs Lörincz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marco Blessmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Henning Hanken
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Arne Böttcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Till Sebastian Clauditz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adrian Münscher.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all participants included in the study.

Additional information

No author has a financial or proprietary interest in any material or method mentioned.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Münscher, A., Prochnow, S., Gulati, A. et al. Survivin expression in head and neck squamous cell carcinomas is frequent and correlates with clinical parameters and treatment outcomes. Clin Oral Invest 23, 361–367 (2019). https://doi.org/10.1007/s00784-018-2444-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-018-2444-8

Keywords

  • Survivin
  • Prognosis
  • Head and neck squamous cell carcinoma (HNSCC)