Skip to main content

Advertisement

Log in

Laryngeal carcinoma lymph node metastasis and disease-free survival correlate with MASPIN nuclear expression but not with EGFR expression: a series of 108 cases

  • Laryngology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Despite advances in laryngeal squamous cell carcinoma (LSCC) treatment, patient survival has not improved in the last two decades. Novel, more effective strategies should be based on receptor-mediated LSCC-targeted therapy. The epidermal growth factor receptor (EGFR) is the most widely studied molecular target. MASPIN multifaceted anti-tumor effects have been rarely evaluated in LSCC. The aims of this study were to investigate EGFR and MASPIN expression and the role of sub-cellular MASPIN localization in LSSC. MASPIN and EGFR expression and the sub-cellular localization of MASPIN were assessed using a computerized image analysis system in 108 consecutive cases of operable LSCC. The rates of occurrence of lymph node metastases and recurrent disease were lower in patients with a nuclear pattern of MASPIN expression (p = 0.004, p = 0.0028). As expected, the loco-regional recurrence rate was lower in N0 patients (p = 0.009), but the disease recurrence rate was even lower in N0 patients with a nuclear localization of MASPIN (p = 0.020). Disease-free survival was longer in cases of LSCC with a nuclear MASPIN pattern (p = 0.003). The intensity of EGFR reactivity and the EGFR area fraction were unrelated to the clinico-pathological and prognostic parameters in LSCC. A nuclear MASPIN pattern is a promising prognostic indicator in LSCC, but further evidence is needed before elective neck dissection can be considered for cN0 LSCCs with a non-nuclear MASPIN pattern. Although a better understanding of the mechanisms behind sub-cellular MASPIN localization is mandatory, re-activating nuclear MASPIN in association with specific chemotherapeutic agents may be an important goal in the treatment of LSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Marioni G, Marchese-Ragona R, Cartei G, Marchese F, Staffieri A (2006) Current opinion in diagnosis and treatment of laryngeal carcinoma. Cancer Treat Rev 32:504–515

    Article  PubMed  Google Scholar 

  2. Wei Q, Sheng L, Shui Y, Hu Q, Nordgren H, Carlsson J (2008) EGFR, HER2, and HER3 expression in laryngeal primary tumors and corresponding metastases. Ann Surg Oncol 15:1193–1201

    Article  PubMed  Google Scholar 

  3. Boonstra J, Rijken P, Humbel B, Cremers F, Verkleij A, van Bergen en Henegouwen P (1995) The epidermal growth factor. Cell Biol Int 19:413–430

    Article  CAS  PubMed  Google Scholar 

  4. West CM, Joseph L, Bhana S (2008) Epidermal growth factor receptor-targeted therapy. Br J Radiol 81(Spec No 1):S36–S44

    Article  PubMed  Google Scholar 

  5. Licitra L, Locati L, Bossi P (2006) Biological agents in head and neck cancer. Ann Oncol 17(Suppl 10):x45–x48

    Article  PubMed  Google Scholar 

  6. Khalkhali-Ellis Z (2006) Maspin: the new frontier. Clin Cancer Res 12:7279–7283

    Article  CAS  PubMed  Google Scholar 

  7. Bailey CM, Khalkhali-Ellis Z, Seftor EA, Hendrix MJ (2006) Biological functions of MASPIN. J Cell Physiol 209:617–624

    Article  CAS  PubMed  Google Scholar 

  8. Lonardo F, Li X, Siddiq F et al (2006) Maspin nuclear localization is linked to favorable morphological features in pulmonary adenocarcinoma. Lung Cancer 51:31–39

    Article  PubMed  Google Scholar 

  9. Marioni G, Staffieri C, Staffieri A, de Filippis C, Blandamura S (2009) MASPIN tumour-suppressing activity in head and neck squamous cell carcinoma. Emerging evidences and therapeutic perspectives. Acta Otolaryngol (Stockh) 129:476–480

    Article  CAS  Google Scholar 

  10. International Union Against Cancer (1997) TNM classification of malignant tumours, 5th edn. Wiley–Liss, New York

    Google Scholar 

  11. Goldstein NS, Armin M (2001) Epidermal growth factor receptor immunohistochemical reactivity in patients with American Joint Committee on Cancer Stage IV colon adenocarcinoma: implications for a standardized scoring system. Cancer 92:1331–1346

    Article  CAS  PubMed  Google Scholar 

  12. Inouè S, Spring KR (1986) Video microscopy. The fundamentals, 2nd edn. Plenum Press, New York

    Google Scholar 

  13. Shannon CE (1949) Communication in the presence of noise. Proc Inst Radio Eng 37:10–21

    Google Scholar 

  14. Dietz A, Boehm A, Mozet C, Wichmann G, Giannis A (2008) Current aspects of targeted therapy in head and neck tumors. Eur Arch Otorhinolaryngol 265(Suppl 1):S3–S12

    Article  PubMed  Google Scholar 

  15. Almadori G, Cadoni G, Galli J et al (1999) Epidermal growth factor receptor expression in primary laryngeal cancer: an independent prognostic factor of neck node relapse. Int J Cancer 84:188–191

    Article  CAS  PubMed  Google Scholar 

  16. Vlachtsis K, Nikolaou A, Markou K, Fountzilas G, Daniilidis I (2005) Clinical and molecular prognostic factors in operable laryngeal cancer. Eur Arch Otorhinolaryngol 262:890–898

    Article  PubMed  Google Scholar 

  17. Jiang H, Yang B-B (2009) p53, epidermal growth factor receptor and proliferating cell nuclear antigen in laryngeal squamous cell carcinoma are not predictive markers for the effect of adjuvant radiotherapy. Acta Otolaryngol (Stockh) 129:101–107

    Article  CAS  Google Scholar 

  18. Pivot X, Magné N, Guardiola E et al (2005) Prognostic impact of epidermal growth factor receptor levels for patients with larynx and hypopharynx cancer. Oral Oncol 41:320–327

    Article  CAS  PubMed  Google Scholar 

  19. Marioni G, Blandamura S, Giacomelli L et al (2005) Nuclear expression of MASPIN is associated with a lower recurrence rate and a longer disease free interval after surgery for squamous cell carcinoma of the larynx. Histopathology 46:576–582

    Article  CAS  PubMed  Google Scholar 

  20. Jang HL, Nam E, Lee KH, Yeom S, Son HJ, Park C (2008) Maspin polymorphism associated with apoptosis susceptibility and in vivo tumorigenesis. Int J Mol Med 22:333–338

    CAS  PubMed  Google Scholar 

  21. Marioni G, D’Alessandro E, Giacomelli L et al (2006) Maspin nuclear localization is related to reduced density of tumour-associated microvessels in laryngeal carcinoma. Anticancer Res 26:4927–4932

    CAS  PubMed  Google Scholar 

  22. Saad RS, Liu YL, Nathan G, Celebrezze J, Medich D, Silverman JF (2004) Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer. Mod Pathol 17:197–203

    Article  CAS  PubMed  Google Scholar 

  23. Marioni G, Ottaviano G, Giacomelli L et al (2006) CD105-assessed micro-vessel density is associated with malignancy recurrence in laryngeal squamous cell carcinoma. Eur J Surg Oncol 32:1149–1153

    Article  CAS  PubMed  Google Scholar 

  24. Marioni G, Giacomelli L, D’Alessandro E et al (2008) Nuclear localization of mammary serine protease inhibitor (MASPIN): is its impact on the prognosis in laryngeal carcinoma due to a pro-apoptotic effect? Am J Otolaryngol 29:156–162

    Article  CAS  PubMed  Google Scholar 

  25. Beltran A, Parikh S, Liu Y et al (2007) Re-activation of a dormant tumor suppressor gene MASPIN by designed transcription factors. Oncogene 26:2791–2798

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Mrs Vincenza Guzzardo, Department of Medical/Diagnostic Sciences and Special Therapies, University of Padova, for her excellent technical assistance and Mrs Frances Coburn for checking the English version of this paper. This study has been supported in part by grant nr 60A07-4404/09 (G.M.) from University of Padova, Italy.

Conflict of interest statement

The authors declare no financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gino Marioni.

Additional information

A preliminary version of this study won the first prize for the Gradenigo–Ferreri–Bilancioni Annual National Award at the Italian Otolaryngological Society (SIO) Meeting, Rimini, 13th–16th May 2009.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marioni, G., Staffieri, A., Bertolin, A. et al. Laryngeal carcinoma lymph node metastasis and disease-free survival correlate with MASPIN nuclear expression but not with EGFR expression: a series of 108 cases. Eur Arch Otorhinolaryngol 267, 1103–1110 (2010). https://doi.org/10.1007/s00405-009-1186-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-009-1186-2

Keywords

Navigation