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Immunohistochemical expression of COX-2 and c-kit in metastatic uveal melanoma

Forums Ocular Melanoma Community Immunohistochemical expression of COX-2 and c-kit in metastatic uveal melanoma

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      metastatic uveal melanoma
      Ana C.A. Frota,* MD; Alexandre N. Odashiro,*† MD, PhD; Patricia R. Pereira,*† MD;
      Bruno F. Fernandes,* MD; Katyanne Dantas Godeiro,* MD;
      Joao Pessoa Souza Filho,*† MD, PhD; Miguel N. Burnier, Jr.,*† MD, PhD
      Case report: We report a case of choroidal melanoma metastatic to the liver diagnosed by fine-needle
      aspiration.The biopsy sample was immunostained for COX-2 and c-kit.
      Comments: Accurate diagnosis and identification of potential therapeutic targets are important for
      subsequent therapy and can be achieved by radiologically guided fine-needle aspiration biopsy.
      Observation : Nous signalons un cas de mélanome choroïdien métastatique au foie, diagnostiqué par
      ponction-biopsie à fine aiguille. L’échantillon obtenu a été immunocoloré pour la COX-2 et le gène c-kit.
      Commentaires : Il importe d’établir un diagnostic précis et d’identifier les cibles thérapeutiques possibles pour
      la thérapie subséquente; la ponction-biopsie à fine aiguille (PBFA) guidée par la radiologie permet d’y parvenir.

      Malignant uveal melanoma (UM) is the most common primary intraocular tumour in adults, and the liver is the most common site for metastases. The use of fine-needle aspiration biopsy (FNAB) for diagnosis of metastatic UM to the liver has been described by Liu et al1 exhibiting successful rates.2,3 Sensitivity reported in the literature ranges from 67% to 100% and specificity from 80% to 100%.4 To our knowledge, the study of immunohistochemical expression of the COX-2 enzyme and c-kit protein and their role in metastatic UM cells obtained by FNAB has never been described.
      A 78-year-old man was referred to the oncology clinic of the Montreal General Hospital, McGill University for
      evaluation of a choroidal mass in his left eye. Fundoscopy revealed a pigmented, well-circumscribed tumour in the
      choroid, displaying low reflectivity on A-scan ultrasound. The tumour measured 9 mm × 6 mm on its basal diameter and 5 mm in height. The diagnosis of choroidal melanoma was established and the patient was treated
      with iodine-125 episcleral brachytherapy. After 3 years, abdominal computerized axial tomography scans
      revealed hepatic, mesentery, and spleen lesions. Liver FNAB under ultrasound guidance confirmed metastatic
      melanoma, epithelioid cell type predominant. Immunohistochemistry for COX-2 and the c-kit protein
      CD117 was performed in the sample, revealing positivity for COX-2 (Fig. 1) and negativity for c-kit.
      COX-2 is a prostaglandin synthase involved in human carcinogenic processes such as angiogenesis, invasion,
      and metastasis.5 The increased expression of COX-2 has been identified in several malignant diseases including
      From *the Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil, and †the Henry C. Witelson Ocular Pathology Laboratory and Registry, McGill University Health Center, Montreal, Que.
      Originally received Dec. 2, 2005. Revised May 29, 2006 Accepted for publication July 13, 2006 Correspondence to: Ana Carolina de Arantes Frota, MD, 3775 University St., Lyman Duff Building, Rm. 216, Montreal, Que.; fax 514-398-5728; [email protected]
      This article has been peer-reviewed. Cet article a été évalué par les pairs.
      Can J Ophthalmol 2007;42:145–6
      doi:10.3129/can j ophthalmol.06-109
      COX-2 and c-kit—Frota et al 145
      Fig. 1—Positive staining for COX-2 in fine-needle aspiration sample of liver metastasis from uveal melanoma (original magnification ×100).
      colorectal cancer,6 cutaneous melanoma,7 and recently, uveal melanoma.8 The presence of COX-2 in mixedcell-
      type UM is correlated to worse prognostic factors.7 The U.S. Food and Drug Administration (FDA)
      approved COX-2 inhibitors for the treatment of patients with familial adenomatous polyposis coli9 and
      epidemiologic studies have shown that these drugs reduce the mortality from colorectal, breast, and lung
      cancer.10 In fact, the use of COX-2 inhibitors warrants investigation as an adjuvant treatment for UM.
      The c-kit protein CD11711,12 is a membrane-bound tyrosinase kinase receptor and its overexpression has been
      observed in several malignancies.13–18 Imatinib mesylate (STI571, Gleevec, Novartis Pharma AG, Basel,
      Switzerland) is a compound that inhibits kinase receptors19 and is FDA-approved for the treatment of c-kit–positive gastrointestinal stromal tumours (GIST) and Philadelphia chromosome-positive chronic myelogenous
      leukemia.20More than 75% of UM cells were shown to be positive for c-kit, and imatinib mesylate decreased the proliferation and invasiveness of different cell lines of human UM.21 These results suggest that the drug may also
      decrease the ability of cells to implant at the metastatic site.
      We conclude that FNAB is not only a diagnostic tool but is also useful in tumour classification with regard to
      COX-2 and c-kit expression. Patients with UM who present with positive staining for COX-2 and c-kit may
      be candidates for tumour therapy with anti–c-kit and COX-2 inhibitors. Currently, the most important goals
      are to increase the quality of life and the survival rates of these patients. These new therapeutic interventions
      could lead to a decrease in cell invasiveness in patients free from metastasis, as well as delaying the on-going
      process in those who already have metastasis, thus reducing the aggressiveness of the disease.
      The authors have no financial conflict of interested regarding this manuscript.

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