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. 1996 Nov;80(11):1009–1012. doi: 10.1136/bjo.80.11.1009

Multidrug resistance in ocular melanoma.

M McNamara 1, M Clynes 1, B Dunne 1, R NicAmhlaoibh 1, W R Lee 1, C Barnes 1, S M Kennedy 1
PMCID: PMC505681  PMID: 8976731

Abstract

AIMS/BACKGROUND: Metastatic disease in patients with ocular melanoma is resistant to chemotherapy. One of the main mechanisms of modulating multidrug resistance is the expression of the multidrug resistance gene 1 (MDR1) product (p-glycoprotein) by tumour cells. The purpose of this study was to evaluate the frequency of expression of the MDR1 gene in ocular melanoma whose primary treatment was surgical excision or enucleation. METHODS: Twelve recent ocular melanomas were received fresh, snap frozen and cryostat sections of tumour were analysed for expression of MDR1 by immunohistochemistry using a well characterised monoclonal antibody to MDR1. Tumour explants were established in short term tissue culture from four tumours and cell blocks were examined by immunohistochemistry. RESULTS: MDR1 expression was present in five of 12 ocular melanomas. Upregulation of protein expression was found in four cell lines established in short term culture from tumour explants. A recurrent tumour, initially treated by local excision and radioactive plaque, showed overexpression of MDR1 mRNA. CONCLUSIONS: These results suggest that significant level of MDR1 may be intrinsically present in ocular melanomas before exposure to drugs involved in multidrug resistance, and indicate the possible importance of MDR1 in modulating chemoresistance in ocular melanoma. Chemosensitisation may be of potential value in planning adjuvant chemotherapy for patients with metastatic disease.

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Selected References

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  1. Baldini N., Scotlandi K., Barbanti-Bròdano G., Manara M. C., Maurici D., Bacci G., Bertoni F., Picci P., Sottili S., Campanacci M. Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med. 1995 Nov 23;333(21):1380–1385. doi: 10.1056/NEJM199511233332103. [DOI] [PubMed] [Google Scholar]
  2. Bedikian A. Y., Kantarjian H., Young S. E., Bodey G. P. Prognosis in metastatic choroidal melanoma. South Med J. 1981 May;74(5):574–577. doi: 10.1097/00007611-198105000-00017. [DOI] [PubMed] [Google Scholar]
  3. De Potter P., Shields C. L., Shields J. A., Cater J. R., Tardio D. J. Impact of enucleation versus plaque radiotherapy in the management of juxtapapillary choroidal melanoma on patient survival. Br J Ophthalmol. 1994 Feb;78(2):109–114. doi: 10.1136/bjo.78.2.109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Einhorn L. H., Burgess M. A., Gottlieb J. A. Metastatic patterns of choroidal melanoma. Cancer. 1974 Oct;34(4):1001–1004. doi: 10.1002/1097-0142(197410)34:4<1001::aid-cncr2820340406>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  5. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  6. Kath R., Hayungs J., Bornfeld N., Sauerwein W., Höffken K., Seeber S. Prognosis and treatment of disseminated uveal melanoma. Cancer. 1993 Oct 1;72(7):2219–2223. doi: 10.1002/1097-0142(19931001)72:7<2219::aid-cncr2820720725>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  7. Kidd M. N., Lyness R. W., Patterson C. C., Johnston P. B., Archer D. B. Prognostic factors in malignant melanoma of the choroid: a retrospective survey of cases occurring in Northern Ireland between 1965 and 1980. Trans Ophthalmol Soc U K. 1986;105(Pt 1):114–121. [PubMed] [Google Scholar]
  8. Levine E. A., Holzmayer T. A., Roninson I. B., Das Gupta T. K. MDR-1 expression in metastatic malignant melanoma. J Surg Res. 1993 Jun;54(6):621–624. doi: 10.1006/jsre.1993.1095. [DOI] [PubMed] [Google Scholar]
  9. McCartney A. C. Pathology of ocular melanomas. Br Med Bull. 1995 Jul;51(3):678–693. doi: 10.1093/oxfordjournals.bmb.a072986. [DOI] [PubMed] [Google Scholar]
  10. McLean M. J., Foster W. D., Zimmerman L. E. Prognostic factors in small malignant melanomas of choroid and ciliary body. Arch Ophthalmol. 1977 Jan;95(1):48–58. doi: 10.1001/archopht.1977.04450010050004. [DOI] [PubMed] [Google Scholar]
  11. Norris M. D., Bordow S. B., Marshall G. M., Haber P. S., Cohn S. L., Haber M. Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. N Engl J Med. 1996 Jan 25;334(4):231–238. doi: 10.1056/NEJM199601253340405. [DOI] [PubMed] [Google Scholar]
  12. O'Driscoll L., Daly C., Saleh M., Clynes M. The use of reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate specific gene expression in multidrug-resistant cells. Cytotechnology. 1993;12(1-3):289–314. doi: 10.1007/BF00744669. [DOI] [PubMed] [Google Scholar]
  13. O'Driscoll L., Kennedy S., McDermott E., Kelehan P., Clynes M. Multiple drug resistance-related messenger RNA expression in archival formalin-fixed paraffin-embedded human breast tumour tissue. Eur J Cancer. 1996 Jan;32A(1):128–133. doi: 10.1016/0959-8049(95)00552-8. [DOI] [PubMed] [Google Scholar]
  14. Rajpal S., Moore R., Karakousis C. P. Survival in metastatic ocular melanoma. Cancer. 1983 Jul 15;52(2):334–336. doi: 10.1002/1097-0142(19830715)52:2<334::aid-cncr2820520225>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  15. Roessner A., Ueda Y., Bockhorn-Dworniczak B., Blasius S., Peters A., Wuisman P., Ritter J., Paulussen M., Jürgens H., Böcker W. Prognostic implication of immunodetection of P glycoprotein in Ewing's sarcoma. J Cancer Res Clin Oncol. 1993;119(4):185–189. doi: 10.1007/BF01624429. [DOI] [PubMed] [Google Scholar]
  16. Schadendorf D., Herfordt R., Czarnetzki B. M. P-glycoprotein expression in primary and metastatic malignant melanoma. Br J Dermatol. 1995 Apr;132(4):551–555. doi: 10.1111/j.1365-2133.1995.tb08710.x. [DOI] [PubMed] [Google Scholar]
  17. Schinkel A. H., Arceci R. J., Smit J. J., Wagenaar E., Baas F., Dollé M., Tsuruo T., Mechetner E. B., Roninson I. B., Borst P. Binding properties of monoclonal antibodies recognizing external epitopes of the human MDR1 P-glycoprotein. Int J Cancer. 1993 Sep 30;55(3):478–484. doi: 10.1002/ijc.2910550326. [DOI] [PubMed] [Google Scholar]
  18. Shammas H. F., Blodi F. C. Prognostic factors in choroidal and ciliary body melanomas. Arch Ophthalmol. 1977 Jan;95(1):63–69. doi: 10.1001/archopht.1977.04450010065005. [DOI] [PubMed] [Google Scholar]
  19. Weinstein R. S., Kuszak J. R., Kluskens L. F., Coon J. S. P-glycoproteins in pathology: the multidrug resistance gene family in humans. Hum Pathol. 1990 Jan;21(1):34–48. doi: 10.1016/0046-8177(90)90073-e. [DOI] [PubMed] [Google Scholar]
  20. Wishart G. C., Plumb J. A., Going J. J., McNicol A. M., McArdle C. S., Tsuruo T., Kaye S. B. P-glycoprotein expression in primary breast cancer detected by immunocytochemistry with two monoclonal antibodies. Br J Cancer. 1990 Nov;62(5):758–761. doi: 10.1038/bjc.1990.373. [DOI] [PMC free article] [PubMed] [Google Scholar]

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