Skip to main content
SpringerLink
Log in

Expression of p16 in sinonasal malignant melanoma

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate the expression of p16 in relation with the histopathologic features and the clinical course in patients with sinonasal melanoma. Thirty-seven sinonasal melanomas were immunostained for p16. Seventeen tumours were investigated for loss of the 9p21 region using interphase fluorescence in situ hybridization (FISH). Twenty-seven melanomas (72.9%) showed loss of p16 expression. All cases with spindle or mixed cytology showed loss of p16, whereas this was present in 50% of epithelioid tumours (p=0.01). Loss of p16 expression was more frequently seen in melanomas with alveolar architecture (87.5%) than in tumours with diffuse architecture (68.9%) (p=0.4). There was no correlation between p16 expression and presence of lymph node or distant metastases (p=0.57 and 0.24, respectively). In addition, p16 status did not influence overall survival (p=0.2). The FISH results were in good agreement with immunohistochemistry: 11 tumours out of 17 showed deletion of the 9p21 region and 10 of these showed loss of protein expression. Loss of p16 expression is a frequent event in sinonasal melanoma and it is mainly related to deletion of 9p21 region. At variance from cutaneous melanoma, loss of p16 is not correlated with the prognosis of patients affected by sinonasal melanoma.

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

Similar content being viewed by others

References

  1. Batsakis JG, Regezi JA, Solomon AR, Rice DH (1982) The pathology of head and neck tumors: mucosal melanomas. Head Neck Surg 4:404–418

    Article  PubMed  CAS  Google Scholar 

  2. Batsakis JG, Cove H (1994) Melanosis, melanocytic hyperplasia, and primary malignant melanoma of the nasal cavity. Cancer 44:1424–1433

    Google Scholar 

  3. Berthelsen A, Andersen AP, Jensen S, Hansen HA (1984) Melanomas of the mucosa in the oral cavity and the upper respiratory passages. Cancer 54:907–912

    Article  PubMed  CAS  Google Scholar 

  4. Chang AE, Karnell LH, Menck HR (1998) The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 83:1664–1678

    Article  PubMed  CAS  Google Scholar 

  5. Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Brocker EB, LeBoit PE, Pinkel D, Bastian BC (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353:2135–2147

    Article  PubMed  CAS  Google Scholar 

  6. Franquemont DW, Mills SE (1991) Sinonasal malignant melanoma. A clinicopathologic and immunohistochemical study of 14 cases. Am J Clin Pathol 96:689–697

    PubMed  CAS  Google Scholar 

  7. Freedman HM, DeSanto LW, Devine KD, Weiland LH (1973) Malignant melanoma of the nasal cavity and paranasal sinuses. Arch Otolaryngol 97:322–325

    PubMed  CAS  Google Scholar 

  8. Hofbauer GF, Boni R, Simmen D, Mihic D, Nestle FO, Burg G, Dummer R (2002) Histological, immunological and molecular features of a nasal mucosa primary melanoma associated with nasal melanosis. Melanoma Res 12:77–82

    Article  PubMed  CAS  Google Scholar 

  9. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS III, Johnson BE, Skolnick MH (1994) A cell cycle regulator potentially involved in genesis of many tumor types. Science 264:436–440

    Article  PubMed  CAS  Google Scholar 

  10. Lund V (1982) Malignant melanoma of the nasal cavity and paranasal sinuses. J Laryngol Otol 96:347–355

    PubMed  CAS  Google Scholar 

  11. Mihic-Probst D, Mnich CD, Oberholzer PA, Seifert B, Sasse B, Moch H, Dummer R (2006). p16 expression in primary malignant melanoma is associated with prognosis and lymph node status. Int J Cancer 118:2262–2268

    Article  PubMed  CAS  Google Scholar 

  12. Padilla Parrado M, Saez Castillo AI, Galan Morales JT, Orradre Romeo JL, Delgado Quero AL, Sanchez Carrion S (2001) Melanoma maligno de fosas nasales. Estudio retrospectivo. Analisis de la expresion de p53 y p16INK4. An Otorrinolaringol Ibero Am 28:303–316

    PubMed  CAS  Google Scholar 

  13. Piccinin S, Doglioni C, Maestro R, Vukosavljevic T, Gasparotto D, D’Orazi C, Boiocchi M (1997) p16/CDKN2 and CDK4 gene mutations in sporadic melanoma development and progression. Int J Cancer 74:26–30

    Article  PubMed  CAS  Google Scholar 

  14. Reed JA, Loganzo F Jr, Shea CR, Walker GJ, Flores JF, Glendening JM, Bogdany JK, Shiel MJ, Haluska FG, Fountain JW et al (1995) Loss of expression of the p16/cyclin-dependent kinase inhibitor 2 tumor suppressor gene in melanocytic lesions correlates with invasive stage of tumor progression. Cancer Res 55:2713–2718

    PubMed  CAS  Google Scholar 

  15. Serrano M, Hannon GJ, Beach D (1993) A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366:704–707

    Article  PubMed  CAS  Google Scholar 

  16. Sharpless NE, Chin L (2003) The INK4a/ARF locus and melanoma. Oncogene 22:3092–3098

    Article  PubMed  CAS  Google Scholar 

  17. Sparrow LE, Eldon MJ, English DR, Heenan PJ (1998) p16 and p21WAF1 protein expression in melanocytic tumors by immunohistochemistry. Am J Dermatopathol 20:255–261

    Article  PubMed  CAS  Google Scholar 

  18. Straume O, Sviland L, Akslen LA (2000). Loss of nuclear p16 protein expression correlates with increased tumor cell proliferation (Ki-67) and poor prognosis in patients with vertical growth phase melanoma. Clin Cancer Res 6:1845–1853

    PubMed  CAS  Google Scholar 

  19. Trapp TK, Fu YS, Calcaterra TC (1987) Melanoma of the nasal and paranasal sinus mucosa. Head Neck Surg 113:1086–1089

    CAS  Google Scholar 

  20. Thompson LD, Wieneke JA, Miettinen M (2003) Sinonasal tract and nasopharyngeal melanomas: a clinicopathologic study of 115 cases with a proposed staging system. Am J Surg Pathol 27:594–611

    Article  PubMed  Google Scholar 

  21. van Dijk M, Sprenger S, Rombout P, Marres H, Kaanders J, Jeuken J, Ruiter D (2003) Distinct chromosomal aberrations in sinonasal mucosal melanoma as detected by comparative genomic hybridization. Genes Chromosomes Cancer 36:151–158

    Article  PubMed  Google Scholar 

  22. Wenig BM, Dulguerov P, Kapadia SB, Prasad ML, Fanburg Smith JC, Thompson LDR (2005) Neuroectodermal tumours. In: Barnes L, Eveson JW, Reichart P, Sidranski D (eds) World Health Organization classification of tumours. Pathology and genetics of head and neck tumours. IARC Press, Lyon, pp 65–75

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Human Pathology and Oncology, University of Florence, Viale G.B. Morgagni 85, 50134, Florence, Italy

    Alessandro Franchi, Daniela Massi, Milena Paglierani & Marco Santucci

  2. Department of Anatomic Pathology, Hospital Clinic, University of Barcelona, Barcelona, Spain

    Llucia Alos & Antonio Cardesa

  3. Institute of Pathology, University of Ljubljana, Ljubljana, Slovenia

    Nina Gale & Nina Zidar

Authors
  1. Alessandro Franchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Llucia Alos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nina Gale
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniela Massi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Milena Paglierani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marco Santucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nina Zidar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Antonio Cardesa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alessandro Franchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Franchi, A., Alos, L., Gale, N. et al. Expression of p16 in sinonasal malignant melanoma. Virchows Arch 449, 667–672 (2006). https://doi.org/10.1007/s00428-006-0288-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-006-0288-0

Keywords

Search

Navigation