Skip to main content

Advertisement

SpringerLink
Log in

A prognostic role for Nm23-H1 in laryngeal carcinoma treated with postoperative radiotherapy: an introductory investigation

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

Abstract

Postoperative RT is generally recommended for laryngeal carcinomas (LSCCs) at high risk of recurrence after surgery. There are currently no clinicopathological parameters available to predict response to such adjuvant RT in LSCC, and only a few potentially predictive biomarkers have been investigated. Nm23-H1 protein is reportedly related to the tumor cells’ metastatic potential, and low Nm23-H1 expression levels in human carcinomas often correlate with a poor prognosis. The novel aim of the present preliminary study was to investigate the prognostic value of Nm23-H1 expression and subcellular localization in a series of patients given postoperative RT for LSCC. A retrospective clinicopathological investigation was conducted at an academic tertiary referral center of 28 consecutive patients given postoperative RT for LSCC. Image analysis of immunohistochemical reactions was performed to measure Nm23-H1 total and nuclear expression levels. Disease-free survival (DFS) was significantly shorter among LSCC patients with total Nm23-H1 levels <50.0 % (p = 0.03); the mean total Nm23-H1 expression was lower in patients with recurrent disease than in patients without it (statistical trend, p = 0.07). The disease recurrence rate was significantly higher (p = 0.021) and the DFS shorter (statistical trend, p = 0.052) among LSCC patients with nuclear Nm23-H1 levels <5.0 %. The locoregional recurrence-risk ratio in LSCC patients with nuclear Nm23-H1 levels <5.0 % was 9.16. Nm23-H1 warrants further investigation of its potential role as a predictive biomarker with a view to providing tailored treatments after surgery, such as combinations of chemotherapy and RT instead of RT alone, in patients whose LSCCs have low or no Nm23-H1 expression.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Bosnar MH, Bago R, Cetković H (2009) Subcellular localization of Nm23/NDPK A and B isoforms: a reflection of their biological function? Mol Cell Biochem 329:63–71

    Article  PubMed  CAS  Google Scholar 

  2. Marino N, Marshall JC, Steeg PS (2011) Protein–protein interactions: a mechanism regulating the anti-metastatic properties of Nm23-H1. Naunyn Schmiedebergs Arch Pharmacol 384:351–362

    Article  PubMed  CAS  Google Scholar 

  3. Backer JM, Mendola CE, Kovesdi I, Fairhurst JL, O’Hara B, Eddy RL Jr, Shows TB, Mathew S, Murty VV, Chaganti RS (1992) Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene 8:497–502

    Google Scholar 

  4. Kaul R, Murakami M, Choudhuri T, Robertson ES (2007) Epstein–Barr virus latent nuclear antigens can induce metastasis in a nude mouse model. J Virol 81:10352–10361

    Article  PubMed  CAS  Google Scholar 

  5. Gilles AM, Presecan E, Vonica A, Lascu I (1991) Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem 15:8784–8789

    Google Scholar 

  6. Tee YT, Chen GD, Lin LY, Ko JL, Wang PH (2006) Nm23-H1: a metastasis-associated gene. Taiwan J Obstet Gynecol 45:107–113

    Article  PubMed  Google Scholar 

  7. Mhawech-Fauceglia P, Dulguerov P, Beck A, Bonet M, Allal AS (2007) Value of ezrin, maspin and nm23-H1 protein expressions in predicting outcome of patients with head and neck squamous-cell carcinoma treated with radical radiotherapy. J Clin Pathol 60:185–189

    Article  PubMed  CAS  Google Scholar 

  8. Kim SH, Lee SY, Park HR, Sung JM, Park AR, Kang S, Kim BG, Choi YP, Kim YB, Cho NH (2011) Nuclear localization of Nm23-H1 in head and neck squamous cell carcinoma is associated with radiation resistance. Cancer 117:1864–1873

    Article  PubMed  Google Scholar 

  9. 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 

  10. Sobin LH, Gospodarowicz MK, Wittekind C (eds) (2009) TNM classification of malignant tumors, 7th edn. Wiley-Blackwell, Oxford

    Google Scholar 

  11. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917

    Article  PubMed  CAS  Google Scholar 

  12. Lera J, Lara PC, Perez S, Cabrera JL, Santana C (1998) Tumor proliferation, p53 expression, and apoptosis in laryngeal carcinoma: relation to the results of radiotherapy. Cancer 83:2493–2501

    Article  PubMed  CAS  Google Scholar 

  13. Jiang H, Yang BB (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 

  14. Jin T, Lin HX, Lin H, Guo LB, Ge N, Cai XY, Sun R, Chen WK, Li QL, Hu WH (2012) Expression TGM2 and BNIP3 have prognostic significance in laryngeal cancer patients receiving surgery and postoperative radiotherapy: a retrospective study. J Trans Med 10:64

    Article  Google Scholar 

  15. Marioni G, Blandamura S, Loreggian L, Koussis H, Lionello M, Giacomelli L, Fasanaro E, Lovato A, Staffieri A (2011) Laryngeal carcinoma prognosis after postoperative radiotherapy correlates with CD105 expression, but not with angiogenin or EGFR expression. Eur Arch Otorhinolaryngol 268:1779–1787

    Article  PubMed  Google Scholar 

  16. Lionello M, Blandamura S, Loreggian L, Ottaviano G, Giacomelli L, Marchese-Ragona R, Velardita C, Staffieri A, Marioni G (2012) High mTOR expression is associated with a worse oncological outcome in laryngeal carcinoma treated with postoperative radiotherapy: a pilot study. J Oral Pathol Med 41:136–140

    Article  PubMed  Google Scholar 

  17. Lee CS, Pirdas A, Lee MW (1996) Immunohistochemical demonstration of the Nm23-H1 gene product in human malignant melanoma and Spitz nevi. Pathology 28:220–224

    Article  PubMed  CAS  Google Scholar 

  18. Sirotkovic-Skerlev M, Krizanac S, Kapitanovic S, Husnjak K, Unusic J, Pavelic K (2005) Expression of c-myc, erb-2, erbB-2, p53 and nm23-H1 gene product in benign and malignant breast lesions: coexpression and correlation with clinicopathologic parameters. Exp Mol Pathol 79:42–50

    Article  PubMed  CAS  Google Scholar 

  19. Kapitanović S, Cacev T, Berković M, Popović-Hadzija M, Radosević S, Seiwerth S, Spaventi S, Pavelić K, Spaventi R (2004) Nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma. J Clin Pathol 57:1312–1318

    Article  PubMed  Google Scholar 

  20. Muller W, Schneiders A, Hommel G, Gabbert HE (1998) Expression of Nm23 in gastric carcinoma: association with tumor progression and poor prognosis. Cancer 83:2481–2487

    Article  PubMed  CAS  Google Scholar 

  21. Zhang ZM, Yang XQ, Wang D, Wang G, Yang ZZ, Qing Y, Yang ZX, Li MX, Xiang DB (2011) Nm23-H1 protein binds to APE1 at AP sites and stimulates AP endonuclease activity following ionizing radiation of the human lung cancer A549 cells. Cell Biochem Biophys 61:561–572

    Article  PubMed  CAS  Google Scholar 

  22. Lee CS, Pirdas-Zivcic A (1994) nm23-H1 protein immunoreactivity in cancers of the gallbladder, extrahepatic bile ducts and ampulla of Vater. Pathology 26:448–452

    Article  PubMed  CAS  Google Scholar 

  23. Cao XJ, Hao JF, Yang XH, Xie P, Liu LP, Yao CP, Xu J (2012) Prognostic value of expression of EGFR and nm23 for locoregionally advanced nasopharyngeal carcinoma. Med Oncol 29:263–271

    Article  PubMed  CAS  Google Scholar 

  24. Lee CS, Redshaw A, Boag G (1996) nm23-H1 protein immunoreactivity in laryngeal carcinoma. Cancer 77:2246–2250

    Article  PubMed  CAS  Google Scholar 

  25. Gunduz M, Ayhan A, Gullu I, Onerci M, Hosal AS, Gursel B, Hosal IN, Firat D (1997) nm23 Protein expression in larynx cancer and the relationship with metastasis. Eur J Cancer 33:2338–2341

    Article  PubMed  CAS  Google Scholar 

  26. Postel EH, Mango SE, Flint SJ (1989) A nuclease hypersensitive element of the human c-myc promoter interacts with a transcription initiation factor. Mol Cell Biol 9:5123–5133

    PubMed  CAS  Google Scholar 

  27. Marioni G, Gaio E, Giacomelli L, Bertolin A, D’Alessandro E, Stramare R, Facco E, Staffieri A, Blandamura S (2008) MASPIN subcellular localization and expression in oral cavity squamous cell carcinoma. Eur Arch Otorhinolaryngol 265:S97–S104

    Article  PubMed  Google Scholar 

  28. Marioni G, Staffieri A, Bertolin A, Giacomelli L, D’Alessandro E, Ottaviano G, Accordi D, Stramare R, de Filippis C, Blandamura S (2010) 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

    Article  PubMed  Google Scholar 

  29. Marshall JC, Collins J, Marino N, Steeg P (2010) The Nm23-H1 metastasis suppressor as a translational target. Eur J Cancer 46:1278–1282

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosciences, Otolaryngology Section, University of Padova, Via Giustiniani 2, 35128, Padua, Italy

    Marco Lionello, Andrea Lovato, Giulia Tealdo, Niccolò Favaretto, Alberto Staffieri & Gino Marioni

  2. Department of Medicine, Anatomic Pathology Section, University of Padova, Padua, Italy

    Stella Blandamura & Luciano Giacomelli

  3. Department of Surgical, Oncological and Gastroenterological Sciences, 2nd Surgical Clinic, University of Padova, Padua, Italy

    Marco Agostini

  4. Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, USA

    Marco Agostini

  5. Istituto di Ricerca Pediatrica, Città della Speranza, Padua, Italy

    Marco Agostini

  6. Department of Neurosciences, Otolaryngology Section, Treviso Branch, University of Padova, Treviso, Italy

    Claudia Staffieri

  7. Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy

    Lucio Loreggian

Authors
  1. Marco Lionello
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stella Blandamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marco Agostini
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Claudia Staffieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrea Lovato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giulia Tealdo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Niccolò Favaretto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Luciano Giacomelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lucio Loreggian
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Alberto Staffieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gino Marioni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gino Marioni.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lionello, M., Blandamura, S., Agostini, M. et al. A prognostic role for Nm23-H1 in laryngeal carcinoma treated with postoperative radiotherapy: an introductory investigation. Eur Arch Otorhinolaryngol 270, 197–203 (2013). https://doi.org/10.1007/s00405-012-2133-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-012-2133-1

Keywords

Search

Navigation