May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
C–Kit Immunoexpression in a Rabbit Model of Uveal Melanoma
Author Affiliations & Notes
  • P.L. Blanco
    Ophthalmology, The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, PQ, Canada
  • E. Achenson
    Ophthalmology, The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, PQ, Canada
  • A.N. Odashiro
    Ophthalmology, The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, PQ, Canada
    Pathology, Federal University of Sao Paulo, Sao Paulo, Brazil
  • P.R. Pereira
    Ophthalmology, The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, PQ, Canada
  • A.S. Sabrosa
    Ophthalmology, The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, PQ, Canada
  • M.N. Burnier, Jr
    Ophthalmology, The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, PQ, Canada
  • Footnotes
    Commercial Relationships  P.L. Blanco, None; E. Achenson, None; A.N. Odashiro, None; P.R. Pereira, None; A.S. Sabrosa, None; M.N. Burnier, Jr., None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3402. doi:
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      P.L. Blanco, E. Achenson, A.N. Odashiro, P.R. Pereira, A.S. Sabrosa, M.N. Burnier, Jr; C–Kit Immunoexpression in a Rabbit Model of Uveal Melanoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3402.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: C–kit protein is a membrane–bound tyrosine kinase receptor (TKR). Following the binding of extracellular growth factors, TKRs initiate specific intracellular signaling pathways. TKRs are known to play an important role in regulating normal and cancer cell growth and differentiation. Their overexpression is associated with aggressive tumor phenotypes and poor patient outcome in various cancers. The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Canada, has recently reported the expression of C–kit in primary human uveal melanoma (UM) cases. We showed that 78.2 % of UM cases express c–kit. The study of c–kit expression in malignant tumors is important as there is a compound (imatinib mesylate) that inhibits TKRs. The aim of this work is to compare the expression of c–kit in the intraocular tumors and the metastatic lesions resulting from a previously described animal model. Methods: The eyes of 16 rabbits bearing intraocular tumors, as well as their lungs and livers were collected upon sacrifice of the animal. Histopathological examination of the specimens showed that all rabbits developed lung metastasis while two of them developed liver metastasis as well. Immunohistochemistry was performed by the standard avidin–biotin–peroxidase complex technique using a rabbit polyclonal antibody against human c–kit (DAKO Cytomation). Two independent pathologists analyzed the slides and classified them as negative or positive for c–kit expression. Additionally, the percentage of positive cells was estimated. Results: All intraocular tumors were positive for c–kit. Most primary tumors (75%) showed a low percentage of positive cells (less than 10%). Twenty five percent of the intraocular tumors analyzed showed a high number of cells expressing c–kit (over 50%). No c–kit expression was found in the metastatic lesions of the lung or liver. Conclusions: Although all primary tumors expressed c–kit at various levels, no metastatic lesions were demonstrated to be positive for c–kit expression. Therefore, we speculate that during the metastatic cascade, cells lose the expression of this protein, as they may no longer need c–kit to actively proliferate in the new metastatic environment. Studies to evaluate the effects of Imatinib mesylate using this animal model are underway.

Keywords: melanoma • tumors • immunohistochemistry 
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