Skip to main content

Advertisement

Log in

Genetic markers of oral malignant melanoma analysed by fluorescence in situ hybridisation (FISH)

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

Abstract

Oral malignant melanoma (OMM) is a rare condition, and our knowledge about morphological and genetic modifications is scanty and incomplete. The aim of this study is to report morphological and fluorescent in situ hybridisation (FISH) data obtained in four cases of OMM. FISH results were also compared with those of cutaneous malignant melanoma (CMM, three cases), desmoplastic cutaneous melanoma (DMM, four cases) and spindle cells cutaneous melanoma (SCCM, one case). All the OMM cases showed a combined radial and vertical growth pattern, with the invasive component characterised by malignant spindle cells intermingled among collagen bundles. Two cases of OMM resulted positively stained with p16, in contrast with frequent loss of immunoreactivity in CMM. Three OMM were suitable for FISH analysis: 9p21 locus was deleted in 1/3, 1p36 resulted deleted 3/3, while EGFR gene showed a relative deletion. Similar genetic alterations were found in DMM and SCMM, but not in CMM. Ultrastructural findings further enhanced differences between OMM and CMM; OMM displayed, mature-staged melanosomes only within in situ component. In conclusion, OMM presents a morphological and genetic profile similar to DMM; and SCCM, however, displays some differences from CMM.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Aguas SC, Quarracino MC, Lence AN, Lanfranchi-Tizeira HE (2009) Primary melanoma of the oral cavity: ten cases and review of 177 cases from literature. Med Oral Patol Oral Cir Bucal 14(6):E265–E271

    PubMed  Google Scholar 

  2. Kato T, Takematsu H, Tomita Y, Takahashi M, Abe R (1987) Malignant melanoma of mucous membranes. A clinicopathologic study of 13 cases in Japanese patients. Arch Dermatol 123(2):216–220

    Article  PubMed  CAS  Google Scholar 

  3. Barker BF, Carpenter WM, Daniels TE, Kahn MA, Leider AS, Lozada-Nur F, Lynch DP, Melrose R, Merrell P, Morton T, Peters E, Regezi JA, Richards SD, Rick GM, Rohrer MD, Slater L, Stewart JC, Tomich CE, Vickers RA, Wood NK, Young SK (1997) Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Western Society of Teachers of Oral Pathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 83(6):672–679

    Article  PubMed  CAS  Google Scholar 

  4. Rákosy Z, Vízkeleti L, Ecsedi S, Vokó Z, Bégány A, Barok M, Krekk Z, Gallai M, Szentirmay Z, Adány R, Balázs M (2007) EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis. Int J Cancer 121(8):1729–1737, 15

    Article  PubMed  Google Scholar 

  5. Poetsch M, Dittberner T, Woenckhaus C (2003) Microsatellite analysis at 1p36.3 in malignant melanoma of the skin: fine mapping in search of a possible tumour suppressor gene region. Melanoma Res 13(1):29–33

    Article  PubMed  CAS  Google Scholar 

  6. Hussein MR, Roggero E, Tuthill RJ, Wood GS, Sudilovsky O (2003) Identification of novel deletion Loci at 1p36 and 9p22-21 in melanocytic dysplastic nevi and cutaneous malignant melanomas. Arch Dermatol 139(6):816–817

    Article  PubMed  Google Scholar 

  7. American Joint Committee on Cancer (2010) Cancer Staging Manual, 7th edn. Springer Pub, London

    Google Scholar 

  8. Smith JS, Perry A, Borell TJ, Lee HK, O'Fallon J, Hosek SM, Kimmel D, Yates A, Burger PC, Scheithauer BW, Jenkins RB (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636–645

    PubMed  CAS  Google Scholar 

  9. Cappuzzo F, Hirsch FR, Rossi E, Bartolini S, Ceresoli GL, Bemis L, Haney J, Witta S, Danenberg K, Domenichini I, Ludovini V, Magrini E, Gregorc V, Doglioni C, Sidoni A, Tonato M, Franklin WA, Crino L, Bunn PA Jr, Varella-Garcia M (2005) Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst 97(9):643–655

    Article  PubMed  CAS  Google Scholar 

  10. Sauer T, Guren MG, Noren T, Dueland S (2005) Demonstration of EGFR gene copy loss in colorectal carcinomas by fluorescence in situ hybridization (FISH): a surrogate marker for sensitivity to specific anti-EGFR therapy? Histopathology 47:560–564

    Article  PubMed  CAS  Google Scholar 

  11. Farnedi A, Magrini E, Betts CM, Cocchi R, Pession A, Foschini MP (2005) Cytogenetic analysis of oral malignant melanoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99(6):655–656

    Article  PubMed  Google Scholar 

  12. Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y, Weaver-Feldhaus J, McClure M, Aitken JF, Anderson DE, Bergman W, Frants R, Goldgar DE, Green A, MacLennan R, Martin NG, Meyer LJ, Youl P, Zone JJ, Skolnick MH, Cannon-Albright LA (1994) Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet 8(1):23–26

    Article  PubMed  CAS  Google Scholar 

  13. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA (1994) Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368(6473):753–756, 21

    Article  PubMed  CAS  Google Scholar 

  14. Talve L, Sauroja I, Collan Y, Punnonen K, Ekfors T (1997) Loss of expression of the p16INK4/CDKN2 gene in cutaneous malignant melanoma correlates with tumor cell proliferation and invasive stage. Int J Cancer 74(3):255–259, 20

    Article  PubMed  CAS  Google Scholar 

  15. Reed JA, Loganzo F Jr, Shea CR, Walker GJ, Flores JF, Glendening JM, Bogdany JK, Shiel MJ, Haluska FG, Fountain JW, Albino AP (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(13):2713–2718, 1

    PubMed  CAS  Google Scholar 

  16. Isshiki K, Seng BA, Elder DE, Guerry D, Linnenbach AJ (1994) Chromosome 9 deletion in sporadic and familial melanomas in vivo. Oncogene 9(6):1649–1653

    PubMed  CAS  Google Scholar 

  17. Chang KW, Lin SC, Chao SY, Kwan PC, Chiu CP, Wong YK (2001) Establishment and characterization of an oral melanoma cell line (ME). Oral Oncol 37(3):301–307

    Article  PubMed  CAS  Google Scholar 

  18. Kay PA, Pinheiro AD, Lohse CM, Pankratz VS, Olsen KD, Lewis JE, Nascimento AG (2004) Desmoplastic melanoma of the head and neck: histopathologic and immunohistochemical study of 28 cases. Int J Surg Pathol 12(1):17–24

    Article  PubMed  Google Scholar 

  19. Kucher C, Zhang PJ, Pasha T, Elenitsas R, Wu H, Ming ME, Elder DE, Xu X (2004) Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi. Am J Dermatopathol 26(6):452–457

    Article  PubMed  Google Scholar 

  20. George E, Polissar NL, Wick M (2010) Immunohistochemical evaluation of p16INK4A, E-cadherin, and cyclin D1 expression in melanoma and Spitz tumors. Am J Clin Pathol 133(3):370–379

    Article  PubMed  Google Scholar 

  21. Tanaka N, Odajima T, Mimura M, Ogi K, Dehari H, Kimijima Y, Kohama G (2001) Expression of Rb, pRb2/p130, p53, and p16 proteins in malignant melanoma of oral mucosa. Oral Oncol 37(3):308–314

    Article  PubMed  CAS  Google Scholar 

  22. Hicks MJ, Flaitz CM (2000) Oral mucosal melanoma: epidemiology and pathobiology. Oral Oncol 36(2):152–169

    Article  PubMed  CAS  Google Scholar 

  23. Batsakis JC, Bauer R, Regezi JA, Campbell T (1979) Desmoplastic melanoma of the maxillary alveolus. J Oral Surg 37(2):107–109

    PubMed  CAS  Google Scholar 

  24. Dallera P, Bertoni F, Marchetti C, Bacchini P (1982) Atypical melanocytic hyperplasia concomitant with malignant desmoplastic melanoma of the oral cavity. Minerva Stomatol 31(2):153–164

    PubMed  CAS  Google Scholar 

  25. Kurihara K, Sanada E, Yasuda S, Yamasaki H (1992) Desmoplastic malignant melanoma of the gingiva. Oral Surg Oral Med Oral Pathol 74(2):201–205

    Article  PubMed  CAS  Google Scholar 

  26. Ueta E, Miki T, Osaki T, Iwata J, Sonobe H (1996) Desmoplastic malignant melanoma of the gingiva: case report and review of the literature. Eur J Cancer B Oral Oncol 32B(6):423–427

    Article  PubMed  CAS  Google Scholar 

  27. Kilpatrick SE, White WL, Browne JD (1996) Desmoplastic malignant melanoma of the oral mucosa. An underret diagn pitfall Cancer 78(3):383–389

    CAS  Google Scholar 

  28. Kavanagh BD, Campbell RL, Patterson JW, O'Neill RL, Cardinale RM, Kaugars GE (2000) Desmoplastic malignant melanoma of the palatal alveolar mucosa: sustained disease-free survival after surgery and postoperative radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 89(4):465–470

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was financed by grants from the Ministry of the University and Research (Fund ex 40% “Fundamental Oriented Research”) and Regione Emilia Romagna (Funds: Region-University Research Program 2007–2009, Project Oncology). ALT is supported with Vanini-Cavagnino grants from the Centro Interdipartimentale di Ricerca sul Cancro “G.Prodi”.

Conflict of interest statement

None declared

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria P. Foschini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baldovini, C., Tosi, A.L., Di Oto, E. et al. Genetic markers of oral malignant melanoma analysed by fluorescence in situ hybridisation (FISH). Virchows Arch 459, 167–173 (2011). https://doi.org/10.1007/s00428-011-1107-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-011-1107-9

Keywords

Navigation