Skip to main content

Advertisement

SpringerLink
Log in

Cyclooxygenase-2 expression in human irradiated uveal melanomas

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Aim

Previous studies have shown that radiotherapy is a stimulus for cyclooxygenase-2 (COX-2) expression and that use of COX-2 inhibitors enhances the radio sensitivity of tumor cells. The objective of this study was to evaluate COX-2 expression, and its correlation with tumor regrowth after irradiation, in enucleated eyes with uveal melanomas.

Methods

Fifteen tissue samples from patients who underwent enucleation after radiotherapy between 1988 and 2001 were used. Nine cases (60%) were enucleated because of tumor regrowth and six (40%) because of severe complications of radiotherapy. Specimens were immunostained for COX-2, and tumor cells were evaluated for specific cytoplasmic and granular immunostaining. COX-2 expression for these cases was compared with that in the previous study including 40 non-irradiated uveal melanoma cases. COX-2 expression was also correlated with tumor regrowth after radiotherapy.

Results

Two cases (13.3%) were positive and thirteen (86.7%) were negative for COX-2 expression. One of the positive cases had been enucleated because of tumor regrowth and one because of radiotherapy complications. There was no relationship between tumor regrowth and COX-2 expression. COX-2 expression was significantly lower in irradiated cases than in non-irradiated cases in the previous study (p < 0.001).

Conclusions

In contrast with studies showing an increase of COX-2 expression in other irradiated malignancies, irradiation was not a factor inducing COX-2 in uveal melanomas. Radiotherapy may, moreover, be a factor that reduces COX-2 expression in uveal melanomas.

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

Similar content being viewed by others

References

  1. Pyo H, Choy H, Amorino GP et al (2001) A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2. Clin Cancer Res 7:2998–3005

    PubMed  CAS  Google Scholar 

  2. Kishi K, Petersen S, Petersen C et al (2000) Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res 60:1326–1331

    PubMed  CAS  Google Scholar 

  3. Hinz B, Brune K (2002) Cyclooxygenase-2–10 years. J of Pharmacol Exp Ther 300:367–375

    Article  CAS  Google Scholar 

  4. Milas L, Mason KA, Liao Z, Ang KK (2003) Chemoradiotherapy: emerging treatment improvement strategies. Head & Neck 25:152–167

    Article  Google Scholar 

  5. Eisengart CA, Mestre JR, Naama HA et al (2000) Prostaglandins regulate melanoma-induced cytokine production in macrophages. Cell Immunol 204:143–149

    Article  PubMed  CAS  Google Scholar 

  6. Xu XC (2002) COX-2 inhibitors in cancer treatment and prevention, a recent development. Anticancer Drugs 13:127–137

    Article  PubMed  CAS  Google Scholar 

  7. Lin TD, Subbaramaiah K, Shah JP, Dannenberg AJ, Boyle JO (2002) Cyclooxygenase-2: A novel molecular target for the prevention and treatment of head and neck cancer. Head & Neck 24:792–798

    Article  Google Scholar 

  8. Gaffney DK, Holden J, Zempolich K, Murphy KJ, Dicker AP, Dodson M (2001) Elevated COX-2 expression in cervical carcinoma. Reduced cause-specific survival and pelvic control. Am J Clin Oncol 24:443–446

    Article  PubMed  CAS  Google Scholar 

  9. Patti R, Gumired K, Reddanna P, Sutton LN, Phillips PC, Reddy CD (2002) Overexpression of cyclooxygenase-2 (COX-2) in human primitive neuroectodermal tumors: effect of celecoxib and rofecoxib. Cancer Lett 180(1):13–21

    Article  PubMed  CAS  Google Scholar 

  10. Denkert C, Kobel M, Berger S et al (2001) Expression of cyclooxygenase-2 in human malignant melanoma. Cancer Res 61:303–308

    PubMed  CAS  Google Scholar 

  11. Kuzbicki L, Sarnecka A, Chwirot BW (2006) Expression of cyclooxygenase-2 in benign naevi and during human cutaneous melanoma progression. Melanoma Res 16(1):29–36

    Article  PubMed  CAS  Google Scholar 

  12. Figueiredo A, Caissie AL, Callejo S, McLean IW, Gold P, Burnier Jr MN (2003) Cyclooxygenase-2 immune-expression in human uveal melanoma: a novel classification of mixed cell type tumors. Can J Ophthalmol 38:352–356

    PubMed  Google Scholar 

  13. Leujeune FJ, Monnier Y, Rüegg C (2006) Complete and long-lasting regression of disseminated multiple skin melanoma metastases under treatment with cyclooxygenase-2 inhibitor. Melanoma Res 16(3):263–265

    Article  CAS  Google Scholar 

  14. Milas L (2001) Cyclooxygenase-2 (COX-2) enzyme inhibitors as potential enhancers of tumor radioresponse. Semin Radiat Oncol 11(4):290–299

    Article  PubMed  CAS  Google Scholar 

  15. Petersen C, Petersen S, Milas L, Lang FF, Tofilon PJ (2000) Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. Clin Cancer Res 6:2513–2520

    PubMed  CAS  Google Scholar 

  16. Steinauer KK, Gibbs I, Ning S, French JN, Armstrong J, Knox SJ (2000) Radiation induces upregulation of cyclooxygenase -2 (COX-2) protein in PC-3 cells. Int J Radiat Oncol Biol Phys 48(2):325–328

    PubMed  CAS  Google Scholar 

  17. Shields CL, Shields JA, Karlsson U, Menduke H, Brady LW (1990) Enucleation after plaque radiotherapy for posterior uveal melanoma. Histopathologic findings. Ophthalmol 97:1665–1670

    CAS  Google Scholar 

  18. Jampol LM, Moy CS, Murray TG et al (2002). The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: IV. Local treatment failure and enucleation in the first 5 years after brachytherapy. COMS report no. 19. Ophthalmology 109:2197–2206

    Article  PubMed  Google Scholar 

  19. Diener-West M, Earle JD, Fine SL, et al, The Collaborative Ocular Melanoma Study (COMS) Group (2001) The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III. Initial mortality findings. COMS Report No. 18. Arch Ophthalmol 119:969–982

  20. The Collaborative Ocular Melanoma Study (COMS) Group (1998) The COMS randomized trial of pre-enucleation radiation of large choroidal melanoma, I: Characteristics of patients enrolled and not enrolled. COMS Report No. 9. Am J Ophthalmol 125:767–778

    Article  Google Scholar 

  21. Zimmerman LE, McLean IW, Foster WD (1978) Does enucleation of the eye containing a malignant melanoma prevent or accelerate the dissemination of tumor cells? Br J Ophthalmol 62:420–425

    Article  PubMed  CAS  Google Scholar 

  22. McLean IW, Foster WD, Zimmerman LE (1980) Inferred natural history of uveal melanoma. Invest Ophthalmol Vis Sci 19:760–770

    PubMed  CAS  Google Scholar 

  23. Messmer E, Bornfeld N, Foerster M, Schilling H, Wessing A (1992) Histopathologic findings in eyes treated with a ruthenium plaque for uveal melanoma. Graefe’s Arch Clin Exp Ophthalmol 230:391–396

    Article  CAS  Google Scholar 

  24. Pe’er J, Stefani FH, Seregard S et al (2001) Cell proliferation activity in posterior uveal melanoma after Ru-106 brachytherapy: an EORTC ocular oncology group study. Br J Ophthalmol 85:1208–1212

    Article  PubMed  CAS  Google Scholar 

  25. Seregard S, Lundell G, Lax I, Trampe E, Kock E (1997) Tumor cell proliferation after failed ruthenium plaque radiotherapy for posterior uveal melanoma. Acta Ophthalmol Scand 75:148–154

    Article  PubMed  CAS  Google Scholar 

  26. Pe’er J, Gnessin H, Shargal Y, Livni N (1994) PC-10 immunostaining of proliferating cell nuclear antigen in posterior uveal melanoma. Enucleation versus enucleation postirradiation groups. Ophthalmology 101:56–62

    PubMed  CAS  Google Scholar 

  27. Chiquet C, Grange JD, Ayzac L, Chauvel P, Patricot LM, Devouassoux-Shisheboran M (2000) Effects of proton beam irradiation on uveal melanoma: a comparative study of expression in irradiated versus non-irradiated melanomas. Br J Ophthalmol 84:98–102

    Article  PubMed  CAS  Google Scholar 

  28. Karlsson M, Boeryd B, Carstensen J, Franlund B, Gustafsson B, Kagedal B (1996) Correlation of Ki-67 and PCNA to DNA ploidy, S-phase fraction and survival in uveal melanoma. Eur J Cancer 32A(2):357–362

    Article  PubMed  CAS  Google Scholar 

  29. Al-Jamal RT, Kivala T (2006) KI-67 immunopositivity in choroidal and ciliary body melanoma with respect to nucleolar diameter and other prognostic factors. Curr Eye Res 31:57–67

    Article  PubMed  CAS  Google Scholar 

  30. Gaffney DK, Holden J, Davis M, Zempolich K, Murphy KJ, Dodson M (2001) Elevated cyclooxygenase-2 expression correlates with diminished survival in carcinoma of the cervix treated with radiotherapy. Int J Radiat Oncol Biol Phys 49:1213–1217

    Article  PubMed  CAS  Google Scholar 

  31. Kim HJ, Wu HG, Park IA, Ha SW (2003) High cyclooxygenase-2 expression is related with distant metastasis in cervical cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys 55(1):16–20

    Article  PubMed  CAS  Google Scholar 

  32. Kim YB, Kim GE, Cho NH et al (2002) Overexpression of cyclooxygenase-2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy. Cancer 95:531–539

    Article  PubMed  CAS  Google Scholar 

  33. Milas L, Kishi K, Hunter N, Mason K, Masferrer JL, Tofilon PJ (1999) Enhancement of tumor response to gamma-radiation by an inhibitor of cyclooxygenase-2 enzyme. J Natl Cancer Inst 91:1501–1504

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sehit Cevdet Özdemir Mah., Seftali Sok.74/17, Dikmen, Ankara, 06450, Turkey

    Pinar Ç. Özdal

  2. The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University Health Center, 3775 University Street, Lyman Duff Room 216, Montreal, QC, Canada, H3A 2B4

    Sonia Callejo, Amanda L. Caissie, Silvin Bakalian, Raul N. G. Vianna & Miguel N. Burnier Jr.

  3. Department of Ophthalmology, McGill University Health Center, Montreal, QC, Canada

    Pinar Ç. Özdal, Chaim Edelstein & Miguel N. Burnier Jr.

  4. Ulucanlar Eye Research Hospital, Ankara, Turkey

    Pinar Ç. Özdal

Authors
  1. Pinar Ç. Özdal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sonia Callejo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Amanda L. Caissie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chaim Edelstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Silvin Bakalian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Raul N. G. Vianna
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Miguel N. Burnier Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pinar Ç. Özdal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Özdal, P.Ç., Callejo, S., Caissie, A.L. et al. Cyclooxygenase-2 expression in human irradiated uveal melanomas. Int Ophthalmol 28, 1–6 (2008). https://doi.org/10.1007/s10792-007-9096-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-007-9096-z

Keywords

Search

Navigation