Immunohistochemistry Characterization of C–Kit Protein in Uveal Melanomas

Abstract

Abstract: : Purpose: Uveal melanoma is the most common primary intraocular tumor in adults. C–kit protein (CD117) is a membrane–bound tyrosine kinase receptor shown to mediate signals for major cellular processes such as proliferation, differentiation, apoptosis, attachment and migration. C–kit overexpression has been observed in Gastrointestinal Stromal Tumors and Philadelphia–chromosome–positive chronic myelogenous leukemia. Recent reports have suggested that c–kit is involved in the pathogenesis of uveal melanoma, although its pattern of immunoexpression has not been elucidated. Moreover, the existence of Imatinib mesylate, a compound that inhibits c–kit receptors, that has been approved by the U.S. FDA to be used as a treatment for specific tumors, makes the investigation of c–kit in uveal melanoma worthwhile. Therefore, the purpose of this study is to report the immunoexpression of c–kit in uveal melanoma. Methods: Fifty–five specimens of primary UM were retrieved from the Henry C. Witelson Ocular Pathology Laboratory and Registry (McGill University, Montreal, Canada). The specimens were analysed regarding histopathological prognostic factors such as cell type, largest tumor dimension, number of mitotic figures, scleral invasion and tumor infiltrating lymphocytes by two pathologists. Immunohistochemistry was performed using the polyclonal anti–CD117 antibody A4502 at a dilution of 1:300. The immunoreactivity was categorized as low, medium or highly positive. C–kit expression in the different UM cell–types (spindle and epithelioid) as well as the pattern of immunoreactivity (cytoplasmic and cell–membrane) were analysed. Results: C–kit expression was positive in 78.2% of the UM cases with low expression in 25.4% medium expression in 16.4%, and high expression in 36.4%. There was no correlation between prognostic factors and c–kit expression. A similar expression in both spindle and epithelioid cell types was found. Of the 78.2% which stained positively, a cytoplasmic and cell–membrane pattern of expression was observed in 100% and 72.8% of the cases respectively. Conclusions: The majority of uveal melanoma cases expressed c–kit ( CD–117). There is no correlation between c–kit expression and histopathological prognostic factors. Because of this high percentage of positivity and the availability of Imatinib mesylate, further studies to investigate the expression of CD–117 in uveal melanoma are justified.

Keywords: melanoma • immunohistochemistry