Progesterone and estrogen receptors in conjunctival melanoma and nevi (original) (raw)

Abstract

Background

Since it has been observed that melanocytic lesions can alter their appearance during pregnancy, we analyzed whether hormone receptors are expressed in conjunctival nevi as well as conjunctival melanoma. We further analyzed whether the number of estrogen (ER) or progesterone receptors (PR) might be associated with the disease course in conjunctival melanoma.

Methods

Twenty-seven paraffin-embedded samples of conjunctival nevi and 27 conjunctival melanoma specimens were examined using immunohistological analysis with antibodies against PR and ER. The percentage of stained cells were analyzed, taking into account patient gender and age. Out of the melanoma group, all patients with complete data for tumor thickness, tumor localization, age at diagnosis, gender, and follow-up including recurrence, metastasis and tumor-related death were included in the second part of the study (n = 15), where hormone receptor rates were associated with tumor outcome, regarding recurrences, metastasis or death. Written consent was received from all included patients.

Results

Both nevi and melanomas showed high rates of PR- and ER-positive cells. In Nevi, 64 ± 25 % of cells stained positive for PR and 35 ± 34 % for ER. In melanoma specimens, 68 ± 30 % showed PR and 44 ± 34 % ER expression. Differences between men and women in expression rates were not statistically significant. Out of 15 melanoma patients (nine female, six male), 53 % (five women and three men) experienced 1—4 recurrences, and four patients developed metastases. The median estimated survival time was 12.2 years. A multivariate survival model taking into account known risk factors for prognosis in conjunctival melanoma confirmed tumor location to be an important predictive factor for outcome (p = 0.05). The rate of PR or ER did not show a statistically significant correlation with the disease course in our cohort.

Conclusions

We observed that conjunctival melanocytic lesions express hormone receptors, which could explain why these tumors can alter their appearance under hormonal changes. Regarding the prognosis of conjunctival melanoma, no statistically significant correlation between hormone receptor expression and event-free survival was found in this analysis.

Access this article

Log in via an institution

Subscribe and save

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Tuomaala S, Eskelin S, Tarkkanen A, Kivelä T (2002) Population-based assessment of clinical characteristics predicting outcome of conjunctival melanoma in whites. IOVS 43:3399–3408
    Google Scholar
  2. Yu G-P, Hu D-N, McCormick S, Finger PT (2003) Conjunctival melanoma: is it increasing in the United States? Am J Ophthalmol 135:800–806
    Article PubMed Google Scholar
  3. Damato B, Coupland SE (2009) Management of conjunctival melanoma. Expert Rev Anticancer Ther 9:1227–1239
    Article PubMed Google Scholar
  4. Shields CL (2000) Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients. Trans Am Ophthalmol Soc 98:471–492
    CAS PubMed Central PubMed Google Scholar
  5. Shildkrot Y, Wilson MW (2010) Conjunctival melanoma: pitfalls and dilemmas in management. Curr Opin Ophthalmol 21:380–386
    Article PubMed Google Scholar
  6. Anastassiou G, Heiligenhaus A, Bechrakis N, Bader E, Bornfeld N, Steuhl K-P (2002) Prognostic value of clinical and histopathological parameters in conjunctival melanomas: a retrospective study. Br J Ophthalmol 86:163–167
    Article PubMed Google Scholar
  7. Missotten GS, Keijser S, Keizer RJWD, Wolff-Rouendaal DD (2005) Conjunctival melanoma in the Netherlands: a nationwide study. IOVS 46:75–82
    Google Scholar
  8. Gallagher RP, Elwood JM, Hill GB, Coldman AJ, Threlfall WJ, Spinelli JJ (1985) Reproductive factors, oral contraceptives and risk of malignant melanoma: Western Canada Melanoma Study. Br J Cancer 52:901–907
    Article CAS PubMed Central PubMed Google Scholar
  9. Lea CS, Holly EA, Hartge P, Lee JS, Guerry D, Elder DE, Halpern A, Sagebiel RW, Tucker MA (2007) Reproductive risk factors for cutaneous melanoma in women: a case–control study. Am J Epidemiol 165:505–513
    Article PubMed Google Scholar
  10. Driscoll MS, Grant-Kels JM (2006) Nevi and melanoma in pregnancy. Dermatol Clin 24:199–204
    Google Scholar
  11. Cocconi G, Bella M, Calabresi F, Tonato M, Canaletti R, Boni C, Buzzi F, Ceci G, Corgna E, Costa P, Lottici R, Papadia F, Sofra MC, Bacchi M (1992) Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen. N Engl J Med 327:516–523
    Article CAS PubMed Google Scholar
  12. Gans LA, Lee SF, Lemp MA, Pepose JS (1990) Estrogen and progesterone receptors and human conjunctiva. Am J Ophthalmol 109:474–477
    CAS PubMed Google Scholar
  13. Esmaeli B, Harvey JT, Hewlett B (2000) Immunohistochemical evidence for estrogen receptors in meibomian glands. Ophthalmology 107:180–184
    Article CAS PubMed Google Scholar
  14. Bonini S, Lambiase A, Schiavone M, Centofanti M, Palma LA, Bonini S (1995) Estrogen and progesterone receptors in vernal keratoconjunctivitis. Ophthalmology 102:1374–1379
    Article CAS PubMed Google Scholar
  15. Wickham LA, Gao J, Toda I, Rocha EM, Ono M, Sullivan DA (2000) Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand 78:146–153
    Article CAS PubMed Google Scholar
  16. Fuchsjäger-Mayrl G, Nepp J, Schneeberger C, Sator M, Dietrich W, Wedrich A, Huber J, Tschugguel W (2002) Identification of estrogen and progesterone receptor mRNA expression in the conjunctiva of premenopausal women. IOVS 43:2841–2844
    Google Scholar
  17. Vavilis D, Agorastos T, Vakiani M, Jafetas J, Panidis D, Konstantinidis T, Bontis J (1997) The effect of transdermal estradiol on the conjunctiva in postmenopausal women. Eur J Obstet Gynecol Reprod Biol 72:93–96
    Article CAS PubMed Google Scholar
  18. Pache M, Glatz-Krieger K, Sauter G, Meyer P (2006) Expression of sex hormone receptors and cell cycle proteins in melanocytic lesions of the ocular conjunctiva. Graefes Arch Clin Exp Ophthalmol 244:113–117
    Article CAS PubMed Google Scholar
  19. Foss AJ, Alexander RA, Guille MJ, Hungerford JL, McCartney AC, Lightman S (1995) Estrogen and progesterone receptor analysis in ocular melanomas. Ophthalmology 102:431–435
    Article CAS PubMed Google Scholar
  20. Paridaens DA, Alexander RA, Hungerford JL, McCartney AC (1991) Oestrogen receptors in conjunctival malignant melanoma: immunocytochemical study using formalin fixed paraffin wax sections. J Clin Pathol 44:840–843
    Article CAS PubMed Google Scholar
  21. Spelsberg H, Klueppel M, Reinhard T, Glaeser M, Niederacher D, Beckmann MW, Sundmacher R (2004) Detection of Oestrogen receptors (ER) α and β in conjunctiva, lacrimal gland, and tarsal plates. Eye 18:729–733
    Article CAS PubMed Google Scholar
  22. Auw-Haedrich C, Feltgen N (2003) Estrogen receptor expression in meibomian glands and its correlation with age and dry-eye parameters. Graefes Arch Clin Exp Ophthalmol 241:705–709
    Article CAS PubMed Google Scholar
  23. Werschnik C, Lommatzsch PK (2002) Long-term follow-up of patients with conjunctival melanoma. Am J Clin Oncol 25:248–255
    Article PubMed Google Scholar
  24. Damato B, Coupland SE (2009) An audit of conjunctival melanoma treatment in Liverpool. Eye 23:801–809
    Article CAS PubMed Google Scholar

Download references

Conflict of interest

The authors declare that they have no conflicts of interest relevant to this study.

Author information

Authors and Affiliations

  1. University Eye Hospital Freiburg, Killianstr. 5, 79106, Freiburg im Breisgau, Germany
    Laura Bredow, Lisa Stützel, Daniel Böhringer, Enken Gundlach, Thomas Reinhard & Claudia Auw-Haedrich

Authors

  1. Laura Bredow
  2. Lisa Stützel
  3. Daniel Böhringer
  4. Enken Gundlach
  5. Thomas Reinhard
  6. Claudia Auw-Haedrich

Corresponding author

Correspondence toLaura Bredow.

Additional information

The authors have full control of all primary data and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data upon request.

Rights and permissions

About this article

Cite this article

Bredow, L., Stützel, L., Böhringer, D. et al. Progesterone and estrogen receptors in conjunctival melanoma and nevi.Graefes Arch Clin Exp Ophthalmol 252, 359–365 (2014). https://doi.org/10.1007/s00417-013-2523-0

Download citation

Keywords