Skip to main content

Advertisement

SpringerLink
Log in

Expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 in conjunctival melanomas and clinical implications

  • Clinical Investigation
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in conjunctival melanomas and their correlations with clinicopathologic parameters and prognosis.

Methods

Fourteen conjunctival melanoma tissue samples and nine conjunctival nevus tissue samples were stained immunohistochemically for MMP-2, MMP-9, and TIMP-1. Association of MMP-2, MMP-9, and TIMP-1 expression in melanoma tissues with clinical progression in terms of metastasis, recurrence, mitotic index, thickness, base diameter, and invasion depth was analyzed.

Results

In the melanoma group, 78.6% of samples showed a positive reaction for MMP-2, 85.7% for MMP-9, and 100% for TIMP-1. In the nevus group, 11.1% showed a positive reaction for MMP-2, 66.7% for MMP-9, and 100% for TIMP-1. MMP-2 expression was significantly more induced in conjunctival melanoma than in benign nevi (P = 0.002). In conjunctival melanoma, MMP-9 expression was higher in tumors >1.5 mm thick (P = 0.026) and TIMP-1 expression was higher in recurrent cases (P = 0.03). There was no significant correlation between the expression and metastasis during the follow-up period (mean, 5 years).

Conclusion

MMP-2, MMP-9, and TIMP-1 were expressed in the majority of conjunctival melanomas, and MMP-2 might play a role in the development and clinical behavior of conjunctival 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

Similar content being viewed by others

References

  1. Seregard S, Koch E. Conjunctival malignant melanoma in Sweden 1969–91. Acta Ophthalmol 1992;70:289–296.

    Article  CAS  Google Scholar 

  2. Paridaens AD, Minassian DC, McCartney AC, Hungerford JL. Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases. Br J Ophthalmol 1994;78:252–259.

    Article  CAS  PubMed  Google Scholar 

  3. Norregaard JC, Gerner N, Jensen OA, Prause JU. Malignant melanoma of the conjunctiva: occurrence and survival following surgery and radiotherapy in a Danish population. Graefes Arch Clin Exp Ophthalmol 1996;234:569–572.

    Article  CAS  PubMed  Google Scholar 

  4. Hu DN, Yu G, McCormick SA, Finger PT. Population-based incidence of conjunctival melanoma in various races and ethnic groups and comparison with other melanomas. Am J Ophthalmol 2008;145:418–423.

    Article  PubMed  Google Scholar 

  5. Chau KY, Hui SP, Cheng GP. Conjunctival melanotic lesions in Chinese: comparison with Caucasian series. Pathology 1999;31:199–201.

    Article  CAS  PubMed  Google Scholar 

  6. Lee SB, Au Eong KG, Saw SM, Chan TK, Lee HP. Eye cancer incidence in Singapore. Br J Ophthalmol 2000;84:767–770.

    Article  CAS  PubMed  Google Scholar 

  7. Tuomaala S, Eskelin S, Tarkkanen A, Kivelä T. Population-based assessment of clinical characteristics predicting outcome of conjunctival melanoma in whites. Invest Ophthalmol Vis Sci 2002;43:3399–3408.

    PubMed  Google Scholar 

  8. Missotten GS, Keijser S, De Keizer RJ, De Wolff-Rouendaal D. Conjunctival melanoma in the Netherlands: a nationwide study. Invest Ophthalmol Vis Sci 2005;46:75–82.

    Article  PubMed  Google Scholar 

  9. Shields CL. Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Trans Am Ophthalmol Soc 2000;98:471–492.

    CAS  PubMed  Google Scholar 

  10. Folberg R, McLean IW, Zimmerman LE. Malignant melanoma of the conjunctiva. Hum Pathol 1985;16:136–143.

    Article  CAS  PubMed  Google Scholar 

  11. De Potter P, Shields CL, Shields JA, Menduke H. Clinical predictive factors for development of recurrence and metastasis in conjunctival melanoma: a review of 68 cases. Br J Ophthalmol 1993;77:624–630.

    Article  PubMed  Google Scholar 

  12. Clark WH Jr, Elder DE, Guerry D 4th, Epstein MN, Greene MH, Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol 1984;15:1147–1165.

    Article  PubMed  Google Scholar 

  13. Hofmann UB, Westphal JR, Van Muijen GN, Ruiter DJ. Matrix metalloproteinases in human melanoma. J Invest Dermatol 2000;115:337–344.

    Article  CAS  PubMed  Google Scholar 

  14. Väisänen A, Tuominen H, Kallioinen M, Turpeenniemi-Hujanen T. Matrix-metalloproteinase 2 (72 kD Type IV collagenase) expression occurs in the early stage of human melanocytic tumour progression and may have prognostic value. J Pathol 1996;180:283–289.

    Article  PubMed  Google Scholar 

  15. Simonetti O, Lucarini G, Brancorsini D, et al. Immunohistochemical expression of vascular endothelial growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9 in cutaneous melanocytic lesions. Cancer 2002;95:1963–1970.

    Article  CAS  PubMed  Google Scholar 

  16. El-Shabrawi Y, Ardjomand N, Radner H, Ardjomand N. MMP-9 is predominantly expressed in epithelioid and not spindle cell uveal melanoma. J Pathol 2001;194:201–206.

    Article  CAS  PubMed  Google Scholar 

  17. Väisänen AH, Kallioinen M, Turpeenniemi-Hujanen T. Comparison of the prognostic value of matrix metalloproteinases 2 and 9 in cutaneous melanoma. Hum Pathol 2008;39:377–385.

    Article  PubMed  Google Scholar 

  18. Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 2000;36:1621–1630.

    Article  CAS  PubMed  Google Scholar 

  19. Birkedal-Hansen H, Moore WG, Bodden MK, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 1993;4:197–250.

    CAS  PubMed  Google Scholar 

  20. Kähäri VM, Saarialho-Kere U. Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann Med 1999;31:34–45.

    Article  PubMed  Google Scholar 

  21. Mahabeleshwar GH, Byzova TV. Angiogenesis in melanoma. Semin Oncol 2007;34:555–565.

    Article  CAS  PubMed  Google Scholar 

  22. Folberg R, Pe’er J, Gruman LM, et al. The morphologic characteristics of tumor blood vessels as a marker of tumor progression in primary human uveal melanoma: a matched case control study. Hum Pathol 1992;23:1298–1305

    Article  CAS  PubMed  Google Scholar 

  23. Seftor RE, Seftor EA, Koshikawa N, et al. Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. Cancer Res 2001;61:6322–6327.

    CAS  PubMed  Google Scholar 

  24. Raffetto JD, Khalil RA. Matrix metalloproteinases in venous tissue remodeling and varicose vein formation. Curr Vasc Pharmacol 2008;6:158–172.

    Article  CAS  PubMed  Google Scholar 

  25. Butler GS, Butler MJ, Atkinson SJ, et al. The TIMP2 membrane type 1 metalloproteinase “receptor” regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem 1998;273:871–880.

    Article  CAS  PubMed  Google Scholar 

  26. Becker JC, Nikroo A, Brabletz T, Reisfeld RA. DNA loops induced by cooperative binding of transcriptional activator proteins and preinitiation complexes. Proc Natl Acad Sci U S A 1995;92:9727–9731.

    Article  CAS  PubMed  Google Scholar 

  27. Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 1997;74:111–122.

    CAS  PubMed  Google Scholar 

  28. Schrohl AS, Holten-Andersen MN, Peters HA, et al. Tumor tissue levels of tissue inhibitor of metalloproteinase-1 as a prognostic marker in primary breast cancer. Clin Cancer Res 2004;10:2289–2298.

    Article  CAS  PubMed  Google Scholar 

  29. Møller Sørensen N, Vejgaard Sørensen I, Ørnbjerg Würtz S, et al. Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment. Scand J Gastroenterol 2008;43:774–786.

    Article  PubMed  Google Scholar 

  30. Joo YE, Seo KS, Kim HS, Rew JS, Park CS, Kim SJ. Expression of tissue inhibitors of metalloproteinases (TIMPs) in gastric cancer. Dig Dis Sci 2000;45:114–121.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Kangdong Sacred Heart Hospital, Hallym University School of Medicine, Seoul, Korea

    Hyoung Kyun Kim

  2. Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

    Seoung Wan Chae

  3. Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Kyung In Woo & Yoon-Duck Kim

  4. Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Korea

    Kyung In Woo

Authors
  1. Hyoung Kyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seoung Wan Chae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kyung In Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoon-Duck Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyung In Woo.

About this article

Cite this article

Kim, H.K., Chae, S.W., Woo, K.I. et al. Expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of MMP (TIMP)-1 in conjunctival melanomas and clinical implications. Jpn J Ophthalmol 54, 221–226 (2010). https://doi.org/10.1007/s10384-009-0793-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-009-0793-1

Keywords

Search

Navigation