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.
Similar content being viewed by others
References
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
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
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
West CM, Joseph L, Bhana S (2008) Epidermal growth factor receptor-targeted therapy. Br J Radiol 81(Spec No 1):S36–S44
Licitra L, Locati L, Bossi P (2006) Biological agents in head and neck cancer. Ann Oncol 17(Suppl 10):x45–x48
Khalkhali-Ellis Z (2006) Maspin: the new frontier. Clin Cancer Res 12:7279–7283
Bailey CM, Khalkhali-Ellis Z, Seftor EA, Hendrix MJ (2006) Biological functions of MASPIN. J Cell Physiol 209:617–624
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
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
International Union Against Cancer (1997) TNM classification of malignant tumours, 5th edn. Wiley–Liss, New York
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
Inouè S, Spring KR (1986) Video microscopy. The fundamentals, 2nd edn. Plenum Press, New York
Shannon CE (1949) Communication in the presence of noise. Proc Inst Radio Eng 37:10–21
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
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
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
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
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
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
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
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
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
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
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
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
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
Corresponding author
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
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00405-009-1186-2